Molecular Profile Detail

Filtering

Case insensitive filtering will display rows where any text in any cell matches the filter term
Simple literal full or partial string matches
Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile	Indication/Tumor Type	Response Type	Relevant Treatment Approaches	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ALK I1171T	ganglioneuroblastoma	predicted - sensitive	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma (PMID: 29907598).	29907598
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171T in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	ALK Inhibitor	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 34845836).	34845836
EML4 - ALK ALK I1171T	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798).	25393798
EML4 - ALK ALK I1171T	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534).	25228534
ALK rearrange ALK I1171T	lung adenocarcinoma	resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534).	25228534
ALK rearrange ALK I1171T	lung adenocarcinoma	resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534).	25228534
ALK rearrange ALK I1171T	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304).	29935304
ALK rearrange ALK I1171T	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304).	29935304
EML4 - ALK ALK C1156Y ALK I1171T	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK I1171T ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK I1171T ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK I1171N	Advanced Solid Tumor	decreased response	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK I1171N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	resistant	ALK Inhibitor	Entrectinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	sensitive		Gilteritinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798).	25393798
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
ALK rearrange ALK I1171N	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911).	27565911
ALK rearrange ALK I1171N	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304).	29935304
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534).	29650534
ALK rearrange ALK I1171N ALK L1198F	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534).	29650534
ALK rearrange ALK I1171N ALK D1203N	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	sensitive		Gilteritinib	Preclinical - Pdx	Actionable	In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Preclinical - Pdx	Actionable	In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Preclinical - Pdx	Actionable	In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198H in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK V1180L	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529).	35324529
ALK T1151M	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK T1151M in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK T1151M	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	ALK Inhibitor	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
ALK rearrange ALK T1151M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK demonstrated disease progression following a 15-month partial response to Alecensa (alectinib) treatment, and was found to have acquired ALK L1196Q (PMID: 33209633).	33209633
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633).	33209633
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
ALK F1245V	neuroblastoma	predicted - sensitive	ALK Inhibitor	Entrectinib	Case Reports/Case Series	Actionable	In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment to result in a partial response that lasted 8.3 months in a patient with neuroblastoma harboring ALK F1245V, who remained on treatment for over 3.5 years due to clinical benefit (PMID: 28183697).	28183697
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	predicted - resistant		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 9.2 months in a patient with lung adenocarcinoma harboring EML4-ALK, at disease progression, ALK G1202R and ALK E1154K were identified in biopsies, while ALK G1202R and ALK I1268V were identified in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted rapid disease progression in a patient with lung adenocarcinoma harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK Q1188_L1190del	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in significant metabolic response and stable disease lasting 11 months in an EML4-ALK-positive lung adenocarcinoma patient harboring ALK Q1188_L1190del who had previously progressed on Xalkori (crizotinib) and Zykadia (ceritinib) treatment (PMID: 33887694).	33887694
ALK positive	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 14% (1/7), a disease control rate of 43% (3/7), and a progression-free survival of 1.9 months in pediatric patients with ALK-positive advanced solid tumors other than neuroblastoma, anaplastic large cell lymphoma, or inflammatory myofibroblastic tumor (PMID: 34780709; NCT01742286).	34780709
ALK positive	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in stable disease in a patient with ALK-positive non-small cell lung carcinoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)).	detail...
ALK positive	neuroblastoma	sensitive	ALK Inhibitor	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in partial response in a patient with ALK-positive neuroblastoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)).	detail...
ALK positive	neuroblastoma	predicted - sensitive	ALK Inhibitor	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 20% (6/30; 6 partial response), a disease control rate of 53% (16/30), and a median progression-free survival of 2.4 months in pediatric patients with ALK-positive neuroblastoma (PMID: 34780709; NCT01742286).	34780709
ALK positive	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Phase III	Actionable	In a Phase III trial, patients with previously untreated ALK-positive advanced non-small cell lung cancer treated with Lorbrena (lorlatinib) demonstrated a significantly improved 12-month progression-free survival rate (78% vs 39%; HR=0.28, p<0.001), objective response rate (76%, 113/149 vs 58%, 85/147; OR=2.25), and intracranial response rate (66%, 25/38 vs 20%, 8/40; OR=8.41) compared to patients treated with Xalkori (crizotinib) (PMID: 33207094; NCT03052608).	33207094
ALK positive	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 52% (76/147; all partial responses), and disease control in 93% (137/147) of patients with crizotinib-refractory ALK-positive non-small cell lung cancer, and a median progression-free survival of 9.6 mo., and of the 97 patients with brain metastases, 41% (40) demonstrated a partial response, and of those, 28 (70%) had an intracranial response and 39 (98%) had intracranial disease control (PMID: 31628085; NCT03215693).	31628085
ALK C1156Y ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) and stable disease in 29% (2/7) of patients with ALK-positive non-small cell lung cancer harboring ALK C1156Y (PMID: 31628085; NCT0321569).	31628085
ALK F1174L ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK G1202R ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 33% (2/6, all partial responses) and stable disease in 50% (3/6) of patients with ALK-positive non-small cell lung cancer harboring ALK G1202R (PMID: 31628085; NCT0321569).	31628085
ALK I1171S ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK F1174V ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK L1152R ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK amp ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 56% (5/9, all partial responses) and stable disease in 44% (4/9) of patients with ALK-positive non-small cell lung cancer with ALK amplification (PMID: 31628085; NCT0321569).	31628085
ALK L1196M ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 25% (1/12, all partial responses) and stable disease in 67% (8/12) of patients with ALK-positive non-small cell lung cancer harboring ALK L1196M (PMID: 31628085; NCT0321569).	31628085
ALK L1152V ALK pos	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK mutant	lung non-small cell carcinoma	no benefit	ALK Inhibitor	Belizatinib	Phase I	Actionable	In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488).	31217479
ALK mutant	lung non-small cell carcinoma	no benefit	ALK Inhibitor	Crizotinib + Onalespib	Phase II	Actionable	In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217).	detail...
ALK mut TP53 wild-type	neuroblastoma	sensitive	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783).	26438783
ALK rearrange ALK mut	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer who acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526).	25724526
EML4 - ALK ALK G1202K	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, fourth-line Lorbrena (lorlatinib) treatment resulted in symptom improvement and response in lung disease with a progression-free survival lasting 4 months in an EML4-ALK positive a patient with lung adenocarcinoma patient harboring EML4-ALK and an acquired ALK G1202K, who had previously progressed on Xalkori (crizotinib) and Alecensa (alectinib) treatment (PMID: 33790576).	33790576
ALK F856S	hematologic cancer	sensitive		GSK1838705A	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with GSK1838705A in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Xalkori (crizotinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	ALK Inhibitor	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with TAE684 in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK D1203N	Advanced Solid Tumor	decreased response	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK D1203N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233).	21948233
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	decreased response	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	decreased response	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK C1156Y ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK rearrange ALK D1203N ALK E1210K ALK G1269A	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK D1203N	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304).	29935304
ALK rearrange ALK D1203N	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542).	31358542
EML4 - ALK ALK F1174L ALK D1203N ALK G1269A	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515).	28434515
ALK rearrange ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in disease progression after 5 months of therapy in a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK L1196M, ALK D1203N was detected in the biopsies at disease progression (PMID: 31585938).	31585938
ALK rearrange ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938).	31585938
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	predicted - resistant		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK D1203N and E1210K compound mutation demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK rearrange ALK F1174X	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK F1174X (n=12), with an objective response rate of 42% (5/12; 95% CI 15.0-72.0), a median duration of response not reached (NR), and a median progression-free survival of 7.4 months (95% CI 2.8-NR) (PMID: 30892989; NCT01970865).	30892989
ALK F1245C	neuroblastoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404).	26554404
ALK F1245C	neuroblastoma	resistant	ALK Inhibitor	Crizotinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404).	26554404
ALK F1245C	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404).	26554404
ALK F1245C	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK F1245C	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1245C in an in vitro assay (PMID: 34158340).	34158340
ALK F1245C TP53 wild-type	neuroblastoma	sensitive	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Pdx	Actionable	In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783).	26438783
EML4 - ALK ALK F1245C	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591).	26775591
EML4 - ALK ALK F1245C	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591).	26775591
EML4 - ALK ALK S1206F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK S1206F	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in clinical improvement within one week of therapy, a 30.3% decrease in target lesion and a partial response after 2 months, and an ongoing response after 4 months in a patient with lung adenocarcinoma harboring de novo EML4-ALK-(E5;A20) and ALK S1206F (PMID: 27565908).	27565908
ALK fusion	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Crizotinib	Phase Ib/II	Actionable	In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770).	28787259
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608).	33207094 detail... detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865).	detail... 30413378 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Phase I	Actionable	In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)).	detail...
ALK fusion	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Repotrectinib	Phase I	Actionable	In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116).	detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the brain and spinal cord metastases in a patient with ALK-positive lung adenocarcinoma, who had been previously treated with Xalkori (crizotinib) (PMID: 35373538).	35373538
ALK fusion	anaplastic large cell lymphoma	sensitive	ALK Inhibitor	Crizotinib	FDA approved	Actionable	In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770).	28787259 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516).	detail... detail... 25754348
ALK fusion	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538).	35373538
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693).	31628085
ALK fusion	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Phase I	Actionable	In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007).	detail...
ALK fusion	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival not reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 33.3% (1/3) in patients harboring ALK fusions (PMID: 35395680; NCT02650401).	35395680
ALK fusion	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Phase I	Actionable	In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697).	28183697
ALK fusion	Erdheim-Chester disease	sensitive	ALK Inhibitor	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN Guidelines).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Alectinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangements (PMID: 28586279; NCT02075840).	detail... 28586279 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Alectinib	Phase III	Actionable	In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Alectinib	Phase II	Actionable	In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008))	detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538).	35373538
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Crizotinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140).	25470694 detail... detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573).	28475456 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Phase Ib/II	Actionable	In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716).	24091716
ALK fusion	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).	detail... detail... detail...
ALK fusion ALK T1151dup	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in shrinkage of the pulmonary and uterine lesions in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins), and the patient remained recurrence-free over 1 year of treatment (PMID: 34184417).	34184417
ALK fusion ALK T1151dup	lung non-small cell carcinoma	no benefit	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment did not result in disease control in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins) whose disease progressed after prior Xalkori (crizotinib) and Alecensa (alectinib) treatments (PMID: 34184417).	34184417
ALK fusion ALK S1206Y	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK S1206Y secondary mutation in the context of an ALK fusion was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer (PMID: 22277784).	22277784
ALK fusion ALK G1202R	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Phase I	Actionable	In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)).	detail...
ALK fusion ALK G1202R KIT amp	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784).	22277784
ALK T1151dup	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK T1151dup in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578).	35421578
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578).	35421578
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK T1151dup (referred to as 1151insT) in culture and in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
ALK rearrange ALK T1151dup ALK G1269A	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526).	25724526
ALK negative	anaplastic large cell lymphoma	predicted - sensitive		Brentuximab vedotin	Phase II	Actionable	In a Phase II trial (SGN-35), Adcetris (brentuximab vedotin) treatment resulted in complete remission in 57% (33/58), partial remission in 29% (17/58) of patients with relapsed or refractory systemic anaplastic large cell lymphoma, 72% (42/58) of the patients were ALK-negative (PMID: 22614995; NCT00866047).	22614995
ALK negative	lung non-small cell carcinoma	resistant	ALK Inhibitor	CEP-28122	Preclinical - Cell line xenograft	Actionable	In a preclinical study, ALK negative non-small cell lung carcinoma cells were resistant to CEP-28122 in culture and in cell line xenograft models (PMID: 22203728).	22203728
ALK negative	leukemia	resistant	ALK Inhibitor	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative leukemia cells in culture (PMID: 22203728).	22203728
ALK negative	lymphoma	resistant	ALK Inhibitor	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative lymphoma cells in culture (PMID: 22203728).	22203728
ALK negative	colon carcinoma	resistant	ALK Inhibitor	CEP-28122	Preclinical - Cell line xenograft	Actionable	In a preclinical study, CEP-28122 did not inhibit tumor growth in cell line xenograft models of ALK-negative colon carcinoma (PMID: 22203728).	22203728
ROS1 rearrange ALK neg	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Crizotinib	Phase II	Actionable	In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 rearranged non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021).	detail...
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK T1151K demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215).	28676215
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215).	28676215
ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Repotrectinib (TPX-0005) inhibited ALK G1202R and suppressed tumor growth in cell line xenograft models with ALK G1202R (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Rozlytrek (entrectinib) in culture (PMID: 26939704).	26939704
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells expressing ALK G1201R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503).	30093503 detail...
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) did not effectively inhibit growth of transformed cells expressing EML4-ALK with ALK G1202R in culture, and did not inhibit tumor growth in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079).	24736079
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853).	27780853
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alunbrig (brigatinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	lung cancer	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315).	26144315
EML4 - ALK ALK G1202R	lung cancer	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib + HJC0152	Preclinical - Cell culture	Actionable	In a preclinical study, HJC0152 and Zykadia (ceritinib) combination treatment increased apoptosis and decreased viability and colony formation in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R compared to either drug alone in culture (PMID: 35085771).	35085771
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041).	24675041
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited Alk autophosphorylation and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and resulted in complete tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	NUV-655	Preclinical - Cell culture	Actionable	In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK G1202R in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468).	detail...
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	XMU-MP-5	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1202R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836).	34845836
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited tumor growth in a mouse cell line xenograft model expressing EML4-ALK and ALK G1202R (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	sensitive		HJC0152	Preclinical - Cell culture	Actionable	In a preclinical study, HJC0152 treatment decreased Stat signaling, migration, and invasion in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R in culture (PMID: 35085771).	35085771
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	lung adenocarcinoma	conflicting	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response and 30 months of progression-free survival in a lung adenocarcinoma patient harboring EML4-ALK and de novo ALK G1202R (PMID: 35235872).	35235872
EML4 - ALK ALK G1202R	lung adenocarcinoma	conflicting	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA, experienced disease progression after 2.5 months of Alunbrig (brigatinib) treatment, and only increased allelic frequency of ALK G1202R was detected at disease progression (PMID: 31585938).	31585938
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1198F and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910).	26698910
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304).	29935304
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK G1202R	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Guideline	Actionable	Lorlatinib is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org).	detail...
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684).	28285684
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 37% (17/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468).	27130468
EML4 - ALK ALK F1174V ALK G1202R	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041).	24675041
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK in culture and resulted in only 18% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	predicted - resistant		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	NUV-655	Preclinical - Cell line xenograft	Actionable	In a preclinical study, NUV-655 treatment resulted in decreased growth in cells expressing both EML4-ALK and ALK G1202R and L1196M in culture and resulted in tumor regression in cell-line xenograft models (Cancer Res 2021;81(13_Suppl):Abstract nr 1468).	detail...
ALK rearrange ALK G1202R ALK G1269A	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK G1202R ALK L1204V ALK G1269A	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK V1180L ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304).	29935304
ALK rearrange ALK F1174L ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
ALK rearrange ALK F1174C ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
EML4 - ALK ALK F1174L ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK G1202R compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	NUV-655	Preclinical - Cell culture	Actionable	In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK mutations, G1202R and G1296A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468).	detail...
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R, ALK L1204V, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1204V compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612).	34994612
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612).	34994612
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK developed progressive disease after initial response to Alecensa (alectinib) treatment, post-progression circulating tumor DNA analysis identified the acquisition of ALK V1180L and ALK G1202R, together with TP53 G105V and MYCN E378fs (PMID: 34994612).	34994612
EML4 - ALK ALK C1156Y ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient with EML4-ALK, ALK G1202R, ALK L1196M, and ALK V1180L prior to Lorbrena (lorlatinib) treatment demonstrated loss of the V1180L variant and acquisition of ALK C1156Y following progression on Lorbrena (lorlatinib) (PMID: 31358542).	31358542
ALK L1198F ALK G1202R	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1202R and L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
ALK F1174C	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174C in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated sensitivity to Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C	lung non-small cell carcinoma	resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041).	24675041
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were sensitive to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK F1174C	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174C ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174C ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK rearrange ALK F1174C	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542).	31358542
ALK R1275Q	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK R1275Q in culture (PMID: 26554404).	26554404
ALK R1275Q	neuroblastoma	sensitive	ALK Inhibitor	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 22203728).	22203728
ALK R1275Q	neuroblastoma	sensitive	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783).	26438783
ALK R1275Q	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK R1275Q in an in vitro assay (PMID: 34158340).	34158340
ALK R1275Q	neuroblastoma	sensitive	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in 3 partial responses and 1 stable disease in 7 pediatric patients with neuroblastoma harboring ALK R1275Q (PMID: 34780709; NCT01742286).	34780709
ALK R1275Q	neuroblastoma	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598).	29907598
ALK R1275Q	neuroblastoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and induced rapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404).	26554404
ALK R1275Q	neuroblastoma	no benefit	ALK Inhibitor	Belizatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q did not respond to treatment with Belizatinib (TSR-011) (PMID: 31217479; NCT02048488).	31217479
ALK R1275Q	neuroblastoma	conflicting	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, among the 12 patients harboring ALK R1275Q, 1 achieved a complete response, 2 achieved partial responses, and 2 achieved prolonged stable diseases (PMID: 33568345; NCT00939770).	33568345
ALK R1275Q	neuroblastoma	conflicting	ALK Inhibitor	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404).	26554404
ALK R1275Q	neuroblastoma	conflicting	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598).	29907598
ALK R1275Q	neuroblastoma	conflicting	ALK Inhibitor	Crizotinib	Preclinical	Actionable	In a preclinical study, Xalkori (crizotinib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913).	24811913
ALK R1275Q	neuroblastoma	sensitive		Vandetanib	Preclinical	Actionable	In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913).	24811913
ALK R1275Q	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK F1174L ALK R1275Q	neuroblastoma	predicted - sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring both ALK F1174V and ALK R1275Q stayed on treatment for 3 cycle until disease progression (PMID: 33568345; NCT00939770).	33568345
ALK G1123D ALK F1174L	neuroblastoma	resistant	ALK Inhibitor	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, expression of ALK G1123D in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233).	21948233
ALK L1152R	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1152R in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1152R	lung cancer	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, lung cancer cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Zykadia (ceritinib) treatment in culture (PMID: 31925410).	31925410
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152R	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a brief response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641).	21791641
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641).	21791641
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, demonstrated a partial response following treatment with Zykadia (ceritinib), however, progressed after 4 months and was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule (PMID: 27091190).	27091190
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - sensitive	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule following progression on Xalkori (crizotinib) and Zykadia (ceritinib), and was subsequently treated with Alecensa (alectinib), resulting in a partial response in all disease areas (PMID: 27091190).	27091190
ALK F1174S	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174S in an in vitro assay (PMID: 34158340).	34158340
ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK G1269A	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1269A in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK fusion positive non-small cell lung cancer with ALK G1269A had a partial response to Alecensa (alectinib) treatment (PMID: 26849637).	26849637
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of a Xalkori (crizotinib)-resistant human non-small cell lung cancer cell line harboring an EML-ALK fusion with ALK G1269A in culture and induced tumor regression in cell line xenograft models (PMID: 26849637, PMID: 23344087).	26849637 23344087
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1269A in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 34845836).	34845836
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture, and inhibited tumor growth in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	predicted - resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated a decreased response when treated with Rozlytrek (entrectinib) compared to cells expressing wild-type EML4-ALK (PMID: 26939704).	26939704
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22235099).	22235099
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315).	26144315
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, human lung cancer cell lines harboring EML4-ALK with ALK G1269A demonstrated sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, human lung cancer cell lines expressing ALK G1269A in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated stable disease when treated with Xalkori (crizotinib), but then progressed, and was found to harbor a secondary resistance mutation, ALK G1269A (PMID: 22235099).	22235099
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910).	26698910 27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK G1269A	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087).	23344087
EML4 - ALK ALK L1196M ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK G1269A	lung adenocarcinoma	unknown	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Rozlytrek (entrectinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	lung adenocarcinoma	sensitive	ALK Inhibitor	Lorlatinib + Saracatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring EML4-ALK and acquired ALK C1156Y and G1269A compound mutation in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK F1174L ALK G1269A	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Belizatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK F1174L and ALK G1269A were identified as newly acquired mutations in the pleural effusion from a patient with lung adenocarcinoma harboring an acquired EML4-ALK after his disease progressed on Belizatinib (TSR-011) treatment (PMID: 28434515).	28434515
ALK rearrange ALK G1269A	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified in biopsies at disease progression after 30 months of Xalkori (crizotinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938).	31585938
ALK rearrange ALK G1269A	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1269A (n=9), with an objective response rate of 89% (8/9; 95% CI 52.0-100.0), a median duration of response not reached (NR) (95% CI 5.6-NR), and a median progression-free survival not reached (95% CI 8.2-NR) (PMID: 30892989; NCT01970865).	30892989
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Alecensa (alectinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Xalkori (crizotinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
ALK L1196M	neuroblastoma	predicted - sensitive	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival over 544 days in a pediatric patient with neuroblastoma harboring ALK L1196M (PMID: 34780709; NCT01742286).	34780709
ALK L1196M	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M in an in vitro assay (PMID: 34158340).	34158340
ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, EML4-ALK and ALK L1196M were identified as acquired mutations in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Xalkori (crizotinib) treatment (PMID: 28434515).	28434515
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32).	detail...
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ensartinib	Preclinical	Actionable	In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408).	21613408
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity in culture (PMID: 26939704).	26939704
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315).	26144315
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504).	21502504
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041).	24675041
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853).	27780853
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	XMU-MP-5	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836).	34845836
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910)	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866).	21575866
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 24887559).	24887559
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK L1196M	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195).	20979473
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784).	22277784
ALK rearrange ALK L1196M	lung non-small cell carcinoma	resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a retrospective analysis, four non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK L1196M (PMID: 25724526).	25724526
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 22% (10/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK L1196M (n=12), with an objective response rate of 67% (8/12; 95% CI 35.0-90.0), a median duration of response not reached (NR) (95% CI 5.2-NR), and a median progression-free survival not reached (95% CI 2.8-NR) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in disease progression after 4 months of therapy in a patient with ALK rearranged lung adenocarcinoma, ALK L1196M was detected in the biopsies at disease progression (PMID: 31585938).	31585938
EML4 - ALK ALK I1171S ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174L ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174V ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK I1179V ALK L1196M	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1196M ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK L1196M ALK L1198F	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
ALK R1192P	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK R1192P	malignant pheochromocytoma	predicted - sensitive	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response (PR) after 2 months of therapy and a sustained PR at 10 months in a patient with malignant pheochromocytoma harboring ALK R1192P (PMID: 34371380).	34371380
ALK R1192P	malignant pheochromocytoma	no benefit	ALK Inhibitor	Alectinib + Octreotide	Case Reports/Case Series	Actionable	In a clinical case study, addition of Alecensa (alectinib) to Octreotide treatment did not lead to a response in a patient with malignant pheochromocytoma harboring ALK R1192P, with a radiological stable disease after 1 month of treatment and disease progression after 5 months of treatment (PMID: 34371380).	34371380
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	ALK Inhibitor	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	resistant	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK C1156Y ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	lung adenocarcinoma	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002).	30662002
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	lung adenocarcinoma	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited Alk kinase activity and proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002).	30662002
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y in an in vitro assay (PMID: 34158340).	34158340
ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Biochemical	Actionable	In a preclinical study, ALK C1156Y was sensitive to Alecensa (alectinib) in an in vitro enzyme assay (PMID: 21575866).	21575866
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 24887559).	24887559
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed human cells expressing EML4-ALK with ALK C1156Y were sensitive to Alecensa (alectinib) in culture (PMID: 21575866).	21575866
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed human cells expressing ALK C1156Y in the context of EML4-ALK demonstrated minimal sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated moderate resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK ALK C1156Y were insensitive to Xalkori (crizotinib) as demonstrated by lack of growth inhibition and lack of kinase inhibition in culture (PMID: 21613408).	21613408
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity (PMID: 26939704).	26939704
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	Ensartinib	Preclinical	Actionable	In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408).	21613408
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	no benefit		Luminespib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with an ALK C1156Y secondary Xalkori (crizotinib) resistance mutation did not respond to Luminespib (AUY922) therapy (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	conflicting	ALK Inhibitor	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) demonstrated tumor growth inhibition in xenograft models of a human non-small cell lung cancer cell line harboring EML4-ALK with ALK C1156Y when compared to Xalkori (crizotinib) (PMID: 24675041).	24675041
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	conflicting	ALK Inhibitor	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation C1156Y, did not respond to Zykadia (ceritinib) therapy (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer developed resistance to Xalkori (crizotinib) with the emergence of ALK C1156Y, a secondary resistance mutation (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, ASP3026 inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	WX-0593	Preclinical - Cell culture	Actionable	In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK C1156Y in the context of EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ALK Inhibitor	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 34845836).	34845836
ALK rearrange ALK C1156Y	lung adenocarcinoma	sensitive	ALK Inhibitor	Lorlatinib + Saracatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK C1156Y in culture (PMID: 31585938).	31585938
ALK rearrange ALK C1156Y	lung non-small cell carcinoma	predicted - resistant	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526).	25724526
ALK rearrange ALK C1156Y	lung adenocarcinoma	predicted - resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK C1156Y was identified in biopsies at disease progression after 16 months of Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement, cells derived from patient's tumor were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
ALK rearrange ALK C1156Y ALK L1198F	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	lung non-small cell carcinoma	resistant	ALK Inhibitor	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	lung non-small cell carcinoma	predicted - sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK F1174I	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK F1174V	Advanced Solid Tumor	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK C1156Y ALK L1198F	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
ALK L1198F	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1198F in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive		Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227).	27432227
ALK S1206R	Advanced Solid Tumor	predicted - sensitive	ALK Inhibitor	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206R in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK S1206R	Advanced Solid Tumor	resistant	ALK Inhibitor	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, transformed cells expressing ALK S1206R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911).	22034911
ALK D1091N	neuroblastoma	predicted - sensitive	ALK Inhibitor	Alectinib + Doxorubicin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243).	28455243
ALK D1091N	neuroblastoma	predicted - sensitive	ALK Inhibitor	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243).	28455243
ALK D1091N	neuroblastoma	sensitive	ALK Inhibitor	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851).	26786851
ALK D1091N	neuroblastoma	sensitive	ALK Inhibitor	AZD3463 + Doxorubicin	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243).	28455243
EML4 - ALK ALK F1174L ALK L1198V	lung non-small cell carcinoma	resistant	ALK Inhibitor	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358).	29636358
ALK wild-type	neuroblastoma	resistant	ALK Inhibitor	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404).	26554404
ALK wild-type	breast cancer	predicted - sensitive	ALK Inhibitor	Cisplatin + Dalantercept	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Dalantercept (ACE-041) in combination with Platinol (cisplatin) resulted in decreased tumor growth in cell line xenograft models of breast cancer (PMID: 26373572).	26373572
ALK wild-type	Advanced Solid Tumor	sensitive	ALK Inhibitor	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing wild-type ALK in culture and suppressed tumor growth in xenograft models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
ALK wild-type	melanoma	sensitive	ALK Inhibitor	Dalantercept + Doxorubicin	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Dalantercept (ACE-041) in combination with Adria (doxorubicin) resulted in decreased tumor growth in cell line xenograft models of melanoma, with increased efficacy over either agent alone (PMID: 26373572).	26373572
ALK wild-type	endometrial cancer	no benefit	ALK Inhibitor	Dalantercept	Phase II	Actionable	In a Phase II clinical trial, treatment with Dalantercept (ACE-041) did not demonstrate activity as single agent in recurrent or persistent endometrial cancer, with a median progression-free survival (PFS) of 2.1 months, overall survival of 14.5 months, no objective responses, and stable disease in 57% (16/28) of patients (PMID: 25888978).	25888978
ALK wild-type	head and neck cancer	predicted - sensitive	ALK Inhibitor	Cisplatin + Dalantercept	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the addition of Dalantercept (ACE-041) to Platinol (cisplatin) treatment resulted in increased cytoxicity and decreased tumor growth in cell line xenograft models of head and neck cancer (PMID: 26373572).	26373572
ALK wild-type	neuroblastoma	resistant	ALK Inhibitor	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 22203728).	22203728
ALK wild-type TP53 C176F	neuroblastoma	no benefit	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783).	26438783
ALK wild-type TP53 H168R	neuroblastoma	no benefit	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783).	26438783
ALK wild-type TP53 P177T	neuroblastoma	no benefit	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783).	26438783
ALK wild-type TP53 mut	neuroblastoma	no benefit	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783).	26438783
ALK wild-type TP53 wild-type	neuroblastoma	no benefit	ALK Inhibitor	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783).	26438783
ALK A348D	hematologic cancer	sensitive	ALK Inhibitor	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Xalkori (crizotinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive		GSK1838705A	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with GSK1838705A in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	ALK Inhibitor	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with TAE684 in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	ALK Inhibitor	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	ALK Inhibitor	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286).	34780709
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223).	34036223
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in a partial response in 3 of 7 pediatric patients with ALK-rearranged inflammatory myofibroblastic tumors, and 3 of the 7 patients achieved stable disease (PMID: 23598171; NCT00939770).	23598171
ALK rearrange	lung non-small cell carcinoma	no benefit	ALK Inhibitor	Belizatinib	Phase I	Actionable	In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488).	31217479
ALK rearrange	epithelioid inflammatory myofibroblastic sarcoma	predicted - sensitive	ALK Inhibitor	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223).	34036223
ALK rearrange	anaplastic large cell lymphoma	sensitive	ALK Inhibitor	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit		Gefitinib	Guideline	Actionable	EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as preferred first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117).	26438117
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Clinical Study	Actionable	In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304).	29935304
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Phase Ib/II	Actionable	In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461).	27836716
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).	detail... detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573).	detail... 28475456
ALK rearrange	lung non-small cell carcinoma	sensitive	ALK Inhibitor	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org).	32169226 detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	ALK Inhibitor	Lorlatinib	Guideline

Profile Name	ALK Y1278S
Gene Variant Detail	ALK Y1278S (gain of function)
Relevant Treatment Approaches	ALK Inhibitor

Molecular Profile Detail

Contact

Filtering

Sorting