Therapy Detail
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| Therapy Name | Crizotinib |
| Synonyms | |
| Therapy Description |
Xalkori (crizotinib), inhibits ALK kinase, ALK fusion proteins, c-Met, ROS1 fusion proteins, and MST1R (RON), resulting in growth inhibition of tumor cells (PMID: 26951079, PMID: 22617245). Xalkori (crizotinib) is FDA approved for use in patients with ALK or ROS1 positive (rearrangements and fusions) non-small cell lung cancer (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Crizotinib | Xalkori | PF-02341066 | ALK Inhibitor 23 MET Inhibitor 52 RON Inhibitor 10 ROS1 Inhibitor 14 | Xalkori (crizotinib), inhibits ALK kinase, ALK fusion proteins, c-Met, ROS1 fusion proteins, and MST1R (RON), resulting in growth inhibition of tumor cells (PMID: 26951079, PMID: 22617245). Xalkori (crizotinib) is FDA approved for use in patients with ALK or ROS1 positive (rearrangements and fusions) non-small cell lung cancer (FDA.gov). |
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- 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"
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| EML4 - ALK ALK V1180L | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534). | 25228534 |
| ALK F1174L | neuroblastoma | resistant | Crizotinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK D1203N | Advanced Solid Tumor | decreased response | 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 |
| NPM1 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). | 25421750 |
| EML4 - ALK SRC pos | lung cancer | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, lung cancer cell lines harboring EML4-ALK and elevated Src activity were resistant to Xalkori (crizotinib) induced growth inhibition in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). | detail... |
| ALK fusion ALK G1202R KIT amp | lung non-small cell carcinoma | predicted - resistant | 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 |
| EML4 - NTRK3 | malignant glioma | predicted - sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Xalkori (crizotinib) resulted in inhibition of cell growth in a glioma cell line harboring EML4-NTRK3 in culture (PMID: 25485619). | 25485619 |
| ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). | 29636358 |
| NPM1 - ALK ALK L1152R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1152R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| NPM1 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| ALK R1275Q | neuroblastoma | conflicting | 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 | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). | 29907598 |
| EML4 - ALK ALK E1303K | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK and ALK E1303K developed progressive disease 7 days after Xalkori (crizotinib) treatment (PMID: 29978950). | 29978950 |
| EML4 - ALK ALK F1174L | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK F1174L in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) in culture (PMID: 27780853). | 27780853 |
| EML4 - ALK ALK F1174L | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). | 27009859 |
| EML4 - ALK ALK C1156Y | lung non-small cell carcinoma | predicted - resistant | 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 |
| NPM1 - ALK ALK I1171T | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK CDKN2A del FGFR1 T141R SMAD4 Q83* | pancreatic ductal adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a pancreatic ductal adenocarcinoma patient harboring EML4-ALK along with CDKN2A deletion, FGFR1 T141R, SMAD4 Q83*, and a TP53 splice site mutation, experienced disease progression after 2 months of Xalkori (crizotinib) treatment, then received Alecensa (alectinib) and remained on treatment for at least 3 months (PMID: 28476735). | 28476735 |
| ALK G1269A ALK rearrange | 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 |
| EML4 - ALK ALK G1269A | lung non-small cell carcinoma | resistant | 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 | lung non-small cell carcinoma | resistant | 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 |
| NPM1 - ALK ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| NPM1 - ALK ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK I1171T | lung non-small cell carcinoma | predicted - resistant | 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 |
| NPM1 - ALK ALK S1206Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| NPM1 - ALK ALK L1196M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| NPM1 - ALK ALK L1196M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). | 25421750 |
| NPM1 - ALK ALK P1139S | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). | 25421750 |
| EML4 - ALK ALK F1174V | lung non-small cell carcinoma | resistant | Crizotinib | Clinical Study | Actionable | In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079). | 24736079 |
| EML4 - ALK ALK L1152P | Advanced Solid Tumor | decreased response | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). | 27780853 |
| EML4 - ALK ALK G1202del | Advanced Solid Tumor | decreased response | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
| NPM1 - ALK ALK F1174L | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| NPM1 - ALK | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). | 25421750 |
| EML4 - ALK HRAS amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, HRAS amplification (PMID: 29636358). | 29636358 |
| ETV6 - NTRK3 | acute myeloid leukemia | sensitive | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited ETV6-NTRK3 activity, reduced cell growth in a human acute myeloid leukemia cell line harboring ETV6-NTRK3, and had anti-tumor activity in xenograft models (PMID: 23811600). | 23811600 |
| EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | resistant | 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 T1151dup | Advanced Solid Tumor | resistant | 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 |
| EML4 - ALK ALK T1151dup | Advanced Solid Tumor | resistant | 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 |
| NPM1 - ALK ALK I1171S | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1161S were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). | 27009859 |
| NPM1 - ALK ALK E1210K | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK E1210K in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK ALK E1154K ALK G1202R ALK I1268V | lung adenocarcinoma | predicted - resistant | 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 |
| NPM1 - ALK ALK T1151M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I trial (PROFILE 1001) that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (38/53), with 6 complete responses and 32 partial responses, a median duration of response of 24.7 months, a median progression-free survival of 19.3 months, and a median overall survival of 51.4 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 30980071; NCT00585195). | detail... detail... 30980071 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Phase II | Actionable | In a Phase II clinical trial, patients with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated an objective response rate of 70% (21/30; all partial response), a median progression-free survival (PFS) of 20 months, a duration of response of 19 months, and a survival rate of 83% at 12 months and 63% at 24 months, when treated with Xalkori (crizotinib) (PMID: 30978502; NCT02183870). | 30978502 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) therapy (PMID: 30715168, PMID: 30285222; ESMO.org). | detail... 30285222 30715168 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as the preferred first-line therapy for ROS1 rearranged non-small cell lung cancer (NCCN.org). | detail... |
| NPM1 - ALK | anaplastic large cell lymphoma | sensitive | Crizotinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). | 28787259 |
| NPM1 - ALK | anaplastic large cell lymphoma | sensitive | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited cell growth, Alk phosphorylation, downstream signaling and induced apoptosis in human anaplastic large cell lymphoma cell lines harboring a NPM1-ALK fusion in culture and in xenograft models (PMID: 18089725). | 18089725 |
| EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | 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 |
| Unknown unknown | alveolar soft part sarcoma | not applicable | Crizotinib | Phase II | Actionable | In a Phase II trial, Xalkori (crizotinib) treatment resulted in partial response (PR) in 2.5% (1/40) and stable disease (SD) in 87.5% (35/40) of patients with TFE3-rearranged, MET-positive alveolar soft part sarcoma, with a 1-year progression-free survival (PFS) rate of 37.5%, and resulted in PR in 25% (1/4) and SD in 75% (3/4) of patients without TFE3 rearrangement and MET expression, with a 1-year PFS rate of 50% (PMID: 29216400; NCT01524926). | 29216400 |
| EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | 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 I1171N | Advanced Solid Tumor | decreased response | 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 I1171T | Advanced Solid Tumor | decreased response | 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 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | 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). | detail... 25470694 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior (PMID: 30715168, PMID: 30285222; ESMO guidelines). | 30715168 30285222 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Phase III | Actionable | In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). | 27022118 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Phase III | Actionable | In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). | detail... |
| ALK fusion ALK S1206Y | lung non-small cell carcinoma | predicted - resistant | 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 |
| NPM1 - ALK ALK G1269A | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). | 27009859 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a clinical study, non-small cell lung carcinoma patients harboring an EML4-ALK variant 1 (E13; A20, n=19) demonstrated a significantly longer progression-free survival (11.0 vs 4.2 months, p<0.05) compared to patients with a non-variant 1 EML4-ALK fusion (n=16) when treated with Xalkori (crizotinib) (PMID: 27354483). | 27354483 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | Crizotinib | Phase I | Actionable | In a Phase I trial, Xalkori (crizotinib) inhibited tumor growth by at least 30% from baseline in 90% (18/20) of patients with EML4-ALK positive non-small cell lung carcinoma (PMID: 20979469; NCT00585195; NCT00585195). | 20979469 |
| ALK fusion | anaplastic large cell lymphoma | sensitive | Crizotinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). | 28787259 |
| ALK rearrange | anaplastic large cell lymphoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). | detail... |
| EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | 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 L1152R | lung non-small cell carcinoma | resistant | 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 GNAS amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, GNAS amplification (PMID: 29636358). | 29636358 |
| ALK L1196M ALK rearrange | 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 L1196M ALK rearrange | 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 |
| NPM1 - ALK ALK C1156F ALK D1203N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | 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 | 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 | 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 |
| ALK amp | neuroblastoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) was less efficient than Lorlatinib (PF-06463922) to induced growth inhibition in ALK-amplified neuroblastoma cells in culture (PMID: 26554404). | 26554404 |
| ALK T1151dup ALK G1269A ALK rearrange | 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 |
| ROS1 rearrange | lung adenocarcinoma | sensitive | Crizotinib | Phase I | Actionable | In a retrospective analysis of Phase I clinical data, Xalkori (crizotinib) resulted in an objective response rate of 80% (24/30) and a median PFS of 9.1 months in patients with ROS1 rearranged lung adenocarcinoma (PMID: 25667280). | 25667280 |
| NPM1 - ALK ALK L1122V ALK L1196M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). | 25421750 |
| ALK neg ROS1 rearrange | lung non-small cell carcinoma | sensitive | 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 DDR2 amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, DDR2 amplification (PMID: 29636358). | 29636358 |
| NPM1 - ALK ALK amp NPM1 amp | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). | 25421750 |
| EML4 - ALK ALK F1245C | 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 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 C1156Y ALK L1196M | lung adenocarcinoma | predicted - resistant | 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 A348D | hematologic cancer | sensitive | 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 |
| EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | sensitive | 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 |
| ROS1 fusion ERBB2 amp FGFR3 amp RET amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of ERBB2 (HER2), FGFR3, and RET (PMID: 29636358). | 29636358 |
| EML4 - ALK ALK S1206Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| NPM1 - ALK ALK I1171N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Xalkori (critzotinb) in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | 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 |
| NPM1 - ALK ALK S1206C | Advanced Solid Tumor | decreased response | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK ALK S1206C to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). | 25421750 |
| NPM1 - ALK ALK F1174V ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F in culture (PMID: 25421750). | 25421750 |
| ALK F1174V ALK amp | neuroblastoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). | 29907598 |
| ALK E1210K ALK rearrange | 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 S1206Y ALK rearrange | 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 S1206Y ALK rearrange | 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 |
| EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | sensitive | 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 |
| NPM1 - ALK ALK R1192P | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Xalkori (Crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| NPM1 - ALK ALK G1128S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). | 25749034 |
| ROS1 fusion KDR amp KIT amp PDGFRA amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of KIT, KDR, and PDGFRA (PMID: 29636358). | 29636358 |
| NPM1 - ALK ALK C1156Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1269A | Advanced Solid Tumor | resistant | 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 | resistant | 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 | 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 |
| ALK F1174L ALK L1198P | neuroblastoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to Xalkori (crizotinib) in culture (PMID: 21948233). | 21948233 |
| ROS1 fusion ROS1 L1951R ROS1 L2026M | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion progressed after 17 months of treatment with Xalkori (crizotinib), and was found to have acquired two additional mutations in trans, ROS1 L2026M and ROS1 L1951R, and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358). | 29636358 |
| NPM1 - ALK ALK F1174I | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK ALK L1152R | Advanced Solid Tumor | resistant | 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 | 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 |
| EML4 - ALK ALK E1210K | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). | 29636358 |
| EML4 - ALK ALK C1156Y | Advanced Solid Tumor | resistant | 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 | 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 | 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 | neuroblastoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing EML4-ALK in culture (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | 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 |
| ALK fusion | lung non-small cell carcinoma | sensitive | 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 | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK fusion (PMID: 30715168, PMID: 30285222; ESMO.org). | 30285222 30715168 detail... |
| EML4 - ALK ALK C1156Y ALK G1269A | Advanced Solid Tumor | resistant | 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 |
| NPM1 - ALK ALK L1196Q | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK containing ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). | 25749034 |
| NPM1 - ALK ALK L1196M ALK D1203N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). | 25421750 |
| ALK amp ALK rearrange | 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 amp ALK rearrange | 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 |
| EML4 - ALK ALK D1203N ALK E1210K | Advanced Solid Tumor | decreased response | 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 I1171S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
| EML4 - ALK ALK L1196M | lung adenocarcinoma | predicted - resistant | 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 |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). | detail... |
| EML4 - ALK ALK L1196M ALK G1269A | lung non-small cell carcinoma | predicted - resistant | 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 |
| NPM1 - ALK ALK C1156F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK C1156F in culture (PMID: 25749034). | 25749034 |
| EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | sensitive | 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 L1198P | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233). | 21948233 |
| EML4 - ALK | inflammatory myofibroblastic tumor | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with inflammatory myofibroblastic tumor harboring EML4-ALK achieved complete remission three years after starting Xalkori (crizotinib) treatment (PMID: 26808369). | 26808369 |
| EML4 - ALK ALK L1196M | Advanced Solid Tumor | resistant | 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 | 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 | 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 |
| ALK L1196M ALK rearrange | 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 |
| EML4 - ALK ALK F1174C | Advanced Solid Tumor | resistant | 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 |
| ROS1 fusion KIT D816G | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion developed resistance to treatment with Xalkori (crizotinib) and was subsequently found to have acquired KIT D816G (PMID: 29636358). | 29636358 |
| PIK3CA E545K ROS1 rearrange | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired a PIK3CA E545K mutation (PMID: 30978502; NCT02183870). | 30978502 |
| ALK F856S | hematologic cancer | sensitive | 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 |
| EML4 - ALK ALK C1156Y ALK L1198F | lung non-small cell carcinoma | predicted - sensitive | 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 F1174V | Advanced Solid Tumor | decreased response | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). | 27780853 |
| NPM1 - ALK ALK R1192P | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK R1192P were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). | 27009859 |
| ALK fusion | inflammatory myofibroblastic tumor | sensitive | 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 F1174L ALK amp | neuroblastoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). | 29907598 |
| EML4 - ALK | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK variant 8 achieved a pathologic complete response following treatment with Xalkori (crizotinib), with a reduction in primary tumor size and pleural metastases within 1 month of treatment, and continuation of treatment for 5 years until death, after which cancer was not observed at autopsy (PMID: 31690489). | 31690489 |
| NPM1 - ALK ALK N1178H | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK N1178H in culture (PMID: 25749034). | 25749034 |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (36/50), with 3 complete responses and 33 partial responses, a median duration of response of 17.6 months, and a median progression-free survival of 19.2 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 25264305; NCT00585195). | detail... 25264305 detail... |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a Phase II trial (NLMT), Xalkori (crizotinib) treatment resulted in an observed objective response rate (ORR) of 71% (5/7), durable clinical benefit rate (DCBR) of 75% (6/8), and medial progression-free survival (PFS) of 44.6 months in patients with non-small cell lung cancer harboring ROS1 fusions, with Bayesian estimated OR and DCBR of 68% and 71%, respectively, and Bayesian posterior probability for OR and DCBR of 0.99 and >0.99, respectively (PMID: 32669708, NCT02664935). | 32669708 |
| EML4 - ALK ALK T1151M | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK T1151M 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 |
| ETV6 - NTRK3 | salivary gland cancer | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in a brief stable disease in a patient with mammary analogue secretory carcinoma of the salivary gland harboring ETV6-NTRK3, before disease progression at 18 weeks (PMID: 26884591). | 26884591 |
| NPM1 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1198F in culture (PMID: 25421750). | 25421750 |
| EML4 - ALK ALK R1192P | Advanced Solid Tumor | sensitive | 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 |
| NPM1 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1202R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| ALK I1171T ALK rearrange | 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 F1245C | neuroblastoma | resistant | 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 |
| NPM1 - ALK ALK I1171T | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, an anaplastic large-cell lymphoma cell line expressing ALK I1171T in the context of NPM1-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24509625). | 24509625 |
| ALK C1156Y ALK rearrange | 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 |
| EML4 - ALK | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). | 30002191 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT01712217 | Phase Ib/II | Crizotinib Onalespib | A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib | Completed |
| NCT00939770 | Phase Ib/II | Crizotinib | Crizotinib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma | Completed |
| NCT02761057 | Phase II | Savolitinib Cabozantinib Crizotinib Sunitinib | Cabozantinib-S-Malate, Crizotinib, Volitinib, or Sunitinib Malate in Treating Patients With Locally Advanced or Metastatic Kidney Cancer | Active, not recruiting |
| NCT02693535 | Phase II | Cobimetinib + Vemurafenib Regorafenib Ipilimumab + Nivolumab Palbociclib Afatinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer | Recruiting |
| NCT01576406 | Phase I | Crizotinib | Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients | Completed |
| NCT00932451 | Phase II | Crizotinib | An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene | Completed |
| NCT02194738 | Phase I | Nivolumab Crizotinib Erlotinib | Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial) | Recruiting |
| NCT03052608 | Phase III | Lorlatinib Crizotinib | A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC | Recruiting |
| NCT01121588 | Phase I | Crizotinib | An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK) | Active, not recruiting |
| NCT02788201 | Phase II | Erlotinib Thiotepa Imatinib Dacarbazine Arsenic trioxide Idarubicin Mitomycin C Thioguanine Mercaptopurine Methotrexate Cladribine Epirubicin Gemcitabine Doxorubicin Bleomycin Etoposide Gefitinib Daunorubicin Lomustine Sorafenib Sunitinib Ifosfamide Asparaginase Ixabepilone Abiraterone Azacitidine Ruxolitinib Decitabine Axitinib Estramustine Floxuridine Lapatinib Carmustine Fludarabine Nilotinib Cisplatin Vismodegib Vandetanib Melphalan Busulfan Carboplatin Toremifene Crizotinib Dactinomycin Temsirolimus Vorinostat Romidepsin Fluorouracil Irinotecan Bortezomib Tamoxifen Topotecan Chlorambucil Pentostatin Eribulin Carfilzomib Vemurafenib Hydroxyurea Exemestane Vincristine Sulfate Dasatinib Mitoxantrone Vinblastine Cytarabine Tretinoin Clofarabine Teniposide Docetaxel Pazopanib Oxaliplatin Streptozocin Paclitaxel Bendamustine Mechlorethamine Mitotane | Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma | Completed |
| NCT02201992 | Phase III | Crizotinib | Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial) | Recruiting |
| NCT03194893 | Phase III | Crizotinib Alectinib | A Roll Over Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer | Recruiting |
| NCT01979536 | Phase II | Crizotinib | Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma | Suspended |
| NCT02511184 | Phase I | Crizotinib Pembrolizumab | Crizotinib Plus Pembrolizumab In Alk-positive Advanced Non Small Cell Lung Cancer Patients | Terminated |
| NCT02465060 | Phase II | Erdafitinib Copanlisib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Pertuzumab + Trastuzumab Dabrafenib + Trametinib Binimetinib Adavosertib Osimertinib Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Larotrectinib Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting |
| NCT03297606 | Phase II | Bosutinib Palbociclib Vismodegib Ipilimumab + Nivolumab Cobimetinib + Vemurafenib Temsirolimus Olaparib Erlotinib Crizotinib Sunitinib Afatinib Dasatinib Pertuzumab + Trastuzumab Axitinib | Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) (CAPTUR) | Recruiting |
| NCT02612194 | Phase II | Crizotinib | LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer | Active, not recruiting |
| NCT03737994 | Phase II | Cisplatin + Lorlatinib Carboplatin + Lorlatinib Ceritinib Alectinib + Cisplatin Alectinib + Carboplatin Ceritinib + Cisplatin Pemetrexed Disodium Carboplatin + Ceritinib Cisplatin + Ensartinib Carboplatin + Ensartinib Brigatinib + Cisplatin Brigatinib Alectinib Brigatinib + Carboplatin Ensartinib Cisplatin + Pemetrexed Disodium Crizotinib Carboplatin + Pemetrexed Disodium Lorlatinib | Biomarker/ALK Inhibitor Combinations in Treating Patients With Stage IV ALK Positive Non-Small Cell Lung Cancer (The NCI-NRG ALK Master Protocol) | Recruiting |
| NCT03126916 | Phase III | Doxorubicin 131I-MIBG Sargramostim Etoposide Melphalan Busulfan Isotretinoin Vincristine Sulfate Cisplatin Cyclophosphamide Thiotepa Crizotinib Dexrazoxane Carboplatin Aldesleukin Topotecan Dinutuximab | Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma | Recruiting |
| NCT02473497 | Expanded access | Crizotinib | Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients | Available |
| NCT02223819 | Phase II | Crizotinib | Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy | Active, not recruiting |
| NCT02551718 | Phase I | Bosutinib Irinotecan Romidepsin Busulfan Melphalan Nilotinib Crizotinib Cytarabine Mitoxantrone Dasatinib Pazopanib Paclitaxel Clofarabine Hydroxyurea Tretinoin Carfilzomib Nelarabine Bexarotene Pentostatin Everolimus Cabozantinib Mercaptopurine Methotrexate Cladribine Thioguanine Daunorubicin Ponatinib Etoposide Afatinib Gefitinib Gemcitabine Regorafenib Arsenic trioxide Trametinib Imatinib Erlotinib Dabrafenib Decitabine Axitinib Azacitidine Ruxolitinib Fludarabine Lapatinib Ceritinib Sirolimus Sorafenib Lomustine Sunitinib Cabazitaxel Temsirolimus Topotecan Bortezomib Pralatrexate | High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia | Recruiting |
| NCT02277457 | Phase I | Crizotinib Erlotinib | Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations | Withdrawn |
| NCT03088930 | Phase II | Crizotinib | Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer | Recruiting |
| NCT01606878 | Phase I | Dexamethasone + Doxorubicin + Vincristine Sulfate Cyclophosphamide + Topotecan Crizotinib | Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma | Completed |
| NCT04084717 | Phase II | Crizotinib | Study of Crizotinib for ROS1 and MET Activated Lung Cancer | Not yet recruiting |
| NCT02584634 | Phase I | Crizotinib Avelumab Lorlatinib | Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101) | Active, not recruiting |
| NCT02737501 | Phase III | Brigatinib Crizotinib | ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Participants (ALTA-1L) | Active, not recruiting |
| NCT02075840 | Phase III | Alectinib Crizotinib | A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants (ALEX) | Active, not recruiting |
| NCT04283669 | Phase II | Crizotinib | Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas (NF110) | Recruiting |
| NCT02559778 | Phase I | Bortezomib Crizotinib Lapatinib Vorinostat Eflornithine Sorafenib Dasatinib | Pediatric Precision Laboratory Advanced Neuroblastoma Therapy | Recruiting |
| NCT01970865 | Phase II | Lorlatinib Crizotinib | A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations | Active, not recruiting |
| NCT02767804 | Phase III | Crizotinib Ensartinib | eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients | Active, not recruiting |
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