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| Gene | ALK |
| Variant | rearrange |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | ALK rearrangement indicates an unspecified rearrangement of the ALK gene. |
| Associated Drug Resistance | |
| Category Variants Paths |
ALK mutant ALK rearrange |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK rearrange ALK I1171T | lung adenocarcinoma | resistant | 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 | 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 | 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 | 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 |
| ALK rearrange ALK I1171T | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK I1171T was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK C1156Y | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | lung adenocarcinoma | sensitive | 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 ALK L1198F | lung non-small cell carcinoma | resistant | 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 |
| ALK rearrange MAP2K1 K57N | lung non-small cell carcinoma | sensitive | Ceritinib + Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). | 25394791 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1202R was identified in 13% (7/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib), and in 32% (18/56) patients who responded to second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | 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 | 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 | predicted - resistant | 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 | sensitive | 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 | Lorlatinib | Guideline | Actionable | Lorbrena (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 - sensitive | Ficonalkib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), a disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 in Chinese patients with ALK-positive non-small cell lung cancer, with an ORR of 70% (7/10) in patients with ALK G1202R (PMID: 38295954; NCT05257512). | 38295954 |
| ALK rearrange RB1 C706F TP53 loss | lung small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). | 28285684 |
| ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - resistant | 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 - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK I1171N was identified in 6% (3/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - sensitive | 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 |
| ALK rearrange ALK G1123S | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). | 26134233 |
| ALK rearrange ALK G1123S | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). | 26134233 |
| ALK rearrange ALK T1151dup ALK G1269A | lung non-small cell carcinoma | predicted - resistant | 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 rearrange ALK amp | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227). | 27432227 |
| ALK rearrange ALK amp | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a retrospective analysis, two 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 amplification (PMID: 25724526). | 25724526 |
| ALK rearrange ALK amp | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK amplification was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) treatment and in 4% (2/56) of patients after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | resistant | 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 | 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 | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK L1196M was identified in one patient with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) and in 27% (15/56) of patients after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | predicted - resistant | 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 - resistant | 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 non-small cell carcinoma | predicted - resistant | 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 | predicted - resistant | 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 | sensitive | 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 | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M (NCCN.org). | detail... |
| ALK rearrange ALK L1196M | lung adenocarcinoma | predicted - resistant | 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 |
| ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | 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 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). | 25724526 |
| ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). | 22277784 |
| ALK rearrange ALK I1171N ALK L1198F | lung non-small cell carcinoma | resistant | 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 | 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 |
| ALK rearrange ALK G1202R ALK G1269A | lung non-small cell carcinoma | resistant | 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 | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R and ALK L1196M developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is not indicated for use as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M and G1202R compound mutations (NCCN.org). | detail... |
| ALK rearrange ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | resistant | 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 D1203N ALK E1210K ALK G1269A | lung non-small cell carcinoma | resistant | 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 V1180L | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). | 29935304 |
| ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK V1180L was identified in 4% (2/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). | 29935304 |
| ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK V1180L was identified in 11% (5/46) 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 V1180L ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 D1203N | lung non-small cell carcinoma | predicted - resistant | 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 | 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 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Crizotinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Ceritinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Alectinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Brigatinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
| ALK rearrange ALK E1210K | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer demonstrated disease progression when treated with Xalkori (crizotinib) due to a secondary acquired resistance mutation, ALK E1210K (PMID: 27432227). | 27432227 |
| ALK rearrange ALK F1174X | lung non-small cell carcinoma | predicted - sensitive | 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 rearrange ALK G1202del | lung non-small cell carcinoma | predicted - sensitive | 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 I1171X | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 26% (12/46) 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 I1171X | lung non-small cell carcinoma | predicted - resistant | Ceritinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 24% (17/70) 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 I1171X | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 24% (17/70) 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 I1171X | lung non-small cell carcinoma | predicted - resistant | Ensartinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 24% (17/70) 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 I1171X | lung non-small cell carcinoma | predicted - sensitive | 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 I1171X (n=8), with an objective response rate of 75% (6/8; 95% CI 35.0-97.0), a median duration of response of 4.2 months (95% CI 2.8-4.2), and a median progression-free survival of 5.5 months (95% CI 4.1-6.9) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK rearrange ALK L1152R | lung adenocarcinoma | predicted - sensitive | 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 rearrange ALK L1152R | lung adenocarcinoma | predicted - resistant | 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 F1174C | lung non-small cell carcinoma | predicted - resistant | 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 rearrange ALK F1174L | lung non-small cell carcinoma | predicted - resistant | 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 rearrange ALK F1174L | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK F1174L was identified in biopsies at disease progression after 4 months of Zykadia (ceritinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938). | 31585938 |
| ALK rearrange ALK F1174L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK F1174L was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK F1174L ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 T1151M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 L1196M ALK D1203N | lung adenocarcinoma | predicted - resistant | 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 | 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 |
| ALK rearrange ALK G1269A | lung adenocarcinoma | predicted - resistant | 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 | 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 |
| ALK rearrange ALK mut | lung non-small cell carcinoma | sensitive | 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 |
| ALK rearrange ROS1 rearrange | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in a near complete response and progression-free survival for at least 55 months in a patient with non-small cell lung cancer harboring rearrangements in ALK and ROS1 (PMID: 34459458). | 34459458 |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size and metabolism in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 28532565). | 28532565 |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size at 3 months in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 30327151). | 30327151 |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in lymph node response and progression-free survival greater than 1 year in a patient with EGFR wild-type lung adenocarcinoma harboring rearrangements in ALK and ROS1 (PMID: 29268402). | 29268402 |
| ALK rearrange ALK L1196Q | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK L1196Q was identified in 4% (2/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK E1129V | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK E1129V was identified in 4% (2/56) of patients with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK I1171S | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK I1171S was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK F1174V | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK F1174V was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK F1174S | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK F1174S was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK T1151R | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK T1151R was identified on post-progression biopsy in a patient with lung adenocarcinoma harboring an ALK rearrangement who had been on Zykadia (ceritinib) treatment for 6 months (PMID: 31027750). | 31027750 |
| ALK rearrange ALK T1151R | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in clinical improvement and a major response in tumor volume and metabolic activity in a patient with metastatic lung adenocarcinoma harboring an ALK rearrangement and ALK T1151R until disease progression 3 months later (PMID: 31027750). | 31027750 |
| ALK rearrange ALK T1151M | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a non-small cell lung cancer patient harboring a non-coding ALK rearrangement with ALK T1151M (PMID: 31446141). | 31446141 |