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 26 MET Inhibitor 53 RON Inhibitor 11 ROS1 Inhibitor 17 | 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, and in pediatric patients 1 year and older and young adults with relapsed or refractory, ALK-positive systemic anaplastic large cell lymphoma (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| EML4 - ALK ALK L1256F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | Crizotinib | FDA approved - On Companion Diagnostic | 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 L1196M ALK L1198F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | 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 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 |
| ROS1 rearrange PIK3CA E545K | 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 |
| 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 |
| 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 |
| 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 |
| ROS1 rearrange ALK neg | 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... |
| 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 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 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 |
| EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 | 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 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 | 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 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 Xalkori (crizotinib) (PMID: 32169226; ESMO.org). | 32169226 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (NCCN.org). | detail... |
| EML4 - ALK ALK D1203N ALK F1245V | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 |
| 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 - ALK ALK L1196Q | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK 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 |
| EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK | 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 |
| EML4 - ALK TP53 V274fs | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274fs were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). | 33310890 |
| ALK F1174L ALK R1275Q | neuroblastoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring both ALK F1174V and ALK R1275Q stayed on treatment for 3 cycle until disease progression (PMID: 33568345; NCT00939770). | 33568345 |
| EML4 - ALK ALK I1171N | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171N | Advanced Solid Tumor | predicted - resistant | 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 |
| ROS1 G2032R | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Biochemical | Actionable | In a preclinical study, Xalkori (crizotinib) treatment did not inhibit kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| 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 |
| 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 | 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 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... |
| EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK 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 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 |
| 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 treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK F1174V | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174V | Advanced Solid Tumor | predicted - resistant | 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 |
| 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 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| 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 |
| 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) in culture (PMID: 33627640). | 33627640 |
| 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 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 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK 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 I1171N ALK L1256F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1152P | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152P demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). | 24675041 |
| EML4 - ALK ALK L1152P | Advanced Solid Tumor | resistant | 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 |
| 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 |
| EML4 - ALK ALK F1245V | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK 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 |
| EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK T1151K | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215). | 28676215 |
| 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 |
| 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 |
| 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 | 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 |
| ALK F1174L | neuroblastoma | no benefit | 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 |
| ALK F1174L | neuroblastoma | no benefit | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). | 33568345 |
| EML4 - ALK ALK D1203N | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK D1203N | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK 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 |
| 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 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 |
| 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 |
| 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 |
| 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 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 ALK C1156Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK C1156Y | Advanced Solid Tumor | 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 I1171N ALK F1174L | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | FDA approved - On Companion Diagnostic | 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 trial (AcSe), treatment with Xalkori (crizotinib) resulted in a an overall response rate after 2 cycles of 47.2% (17/36; all partial responses), and after 4 cycles resulted in a best overall response rate of 69.4% (21/36; 20 partial responses and 1 complete response), and a median progression-free survival of 5.5 months and median overall survival of 17.2 months in patients with ROS1-translocated non-small cell lung cancer (PMID: 31584608; NCT02034981). | 31584608 |
| 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: 32169226; ESMO.org). | detail... 32169226 |
| 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 the preferred first-line therapy for ROS1 rearranged non-small cell lung cancer (NCCN.org). | detail... |
| ROS1 rearrange ROS1 L2026M TP53 P278H | 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 two mutations, ROS1 L2026M and TP53 P278H (PMID: 30978502; NCT02183870). | 30978502 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174I | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 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 G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 |
| 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 |
| EML4 - ALK | colorectal carcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in rapid clinical benefit and a partial response after 1 month of therapy in a patient with metastatic colorectal carcinoma harboring EML4-ALK, until disease progression after 4 months (PMID: 34036227). | 34036227 |
| 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 |
| 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 | Actionable | In a preclinical study, Xalkori (crizotinib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913). | 24811913 |
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, among the 12 patients harboring ALK R1275Q, 1 achieved a complete response, 2 achieved partial responses, and 2 achieved prolonged stable diseases (PMID: 33568345; NCT00939770). | 33568345 |
| 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 |
| 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 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 |
| 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 |
| 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... |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223). | 34036223 |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in a partial response in 3 of 7 pediatric patients with ALK-rearranged inflammatory myofibroblastic tumors, and 3 of the 7 patients achieved stable disease (PMID: 23598171; NCT00939770). | 23598171 |
| 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 |
| 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... |
| ALK rearrange | anaplastic large cell lymphoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). | 28787259 detail... |
| 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 |
| 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 were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK TP53 Q331* | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). | 33310890 |
| 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 |
| 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 |
| 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 - NTRK3 | high grade 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 |
| 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 |
| 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 |
| 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 R1275L | neuroblastoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in stable disease in a pediatric patient with neuroblastoma harboring ALK R1275L who stayed on treatment for 4 cycles (PMID: 23598171; NCT00939770). | 23598171 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK 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 |
| EML4 - ALK | pancreatic cancer | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with treatment lasting eight months in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053). | 34568053 |
| EML4 - ALK ALK I1171T | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK I1171T | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK 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 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 |
| 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 |
| ALK F1174V | neuroblastoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring ALK F1174V stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). | 33568345 |
| 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 T1151K | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK T1151K demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| ALK fusion | anaplastic large cell lymphoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). | 28787259 detail... |
| ROS1 rearrange TP53 mut | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a Phase II clinical trial, treatment with Xalkori (crizotinib) demonstrated a shorter median progression-free survival in patients with non-small cell lung cancer co-harboring a ROS1 rearrangement and TP53 mutation compared to patients with a ROS1 rearrangement and wild-type TP53 (7 vs. 24.1 months; p=0.022) (PMID: 30978502; NCT02183870). | 30978502 |
| ALK fusion | Erdheim-Chester disease | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN Guidelines). | detail... |
| ALK 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 |
| 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 ALK L1196M ALK D1203N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK 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 S1206F | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in clinical improvement within one week of therapy, a 30.3% decrease in target lesion and a partial response after 2 months, and an ongoing response after 4 months in a patient with lung adenocarcinoma harboring de novo EML4-ALK-(E5;A20) and ALK S1206F (PMID: 27565908). | 27565908 |
| EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK S1206R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing ALK S1206R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). | 22034911 |
| 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 |
| 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 |
| 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 treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| 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 |
| 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 |
| 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 G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538). | 35373538 |
| ALK amp | neuroblastoma | no benefit | 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 amp | neuroblastoma | no benefit | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although both patients harboring ALK amplification had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). | 33568345 |
| EML4 - ALK ALK G1269S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). | 22034911 |
| EML4 - ALK ALK G1269S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant 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 |
| 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 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 |
| 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 |
| 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 |
| EML4 - ALK ALK I1171N | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). | 33627640 |
| 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 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| 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 | USA | ITA | FRA | ESP | DEU | CAN | BEL | 14 |
| 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) | Completed | USA | ITA | FRA | ESP | DEU | CAN | AUT | 12 |
| 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 | USA | 0 |
| 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 | USA | ESP | 3 |
| 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 | USA | CAN | 0 |
| 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 | USA | ITA | FRA | ESP | DEU | CAN | BEL | 7 |
| 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) | Recruiting | CAN | 0 |
| NCT03052608 | Phase III | Lorlatinib Crizotinib | A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC | Active, not recruiting | USA | ITA | FRA | ESP | DEU | CAN | BEL | 16 |
| NCT02559778 | Phase I | Bortezomib Crizotinib Lapatinib Vorinostat Eflornithine Sorafenib Dasatinib | Pediatric Precision Laboratory Advanced Neuroblastoma Therapy | Recruiting | USA | 0 |
| 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 | USA | FRA | ESP | CAN | 1 |
| NCT02612194 | Phase II | Crizotinib | LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer | Terminated | USA | 0 |
| NCT02693535 | Phase II | Cobimetinib + Vemurafenib Atezolizumab + Talazoparib Regorafenib Larotrectinib Trastuzumab + Tucatinib Ipilimumab + Nivolumab Palbociclib Afatinib Entrectinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Atezolizumab + Pertuzumab/trastuzumab/hyaluronidase-zzxf 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 (TAPUR) | Recruiting | USA | 0 |
| 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 | Completed | USA | 0 |
| 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 | USA | CAN | 1 |
| NCT04603807 | Phase III | Entrectinib Crizotinib | A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases | Recruiting | ITA | FRA | ESP | 7 |
| 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 | Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer | Active, not recruiting | USA | 0 |
| 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 | USA | ITA | 5 |
| NCT02465060 | Phase II | Erdafitinib Trametinib Crizotinib Sapanisertib AZD4547 Dasatinib Osimertinib Palbociclib Capivasertib Larotrectinib Ulixertinib Nivolumab + Relatlimab Copanlisib Sunitinib Nivolumab Pertuzumab + Trastuzumab Ipatasertib Dabrafenib + Trametinib Binimetinib Adavosertib Afatinib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting | USA | 2 |
| 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 | USA | CAN | 0 |
| NCT01979536 | Phase II | Crizotinib | Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma | Active, not recruiting | USA | 0 |
| NCT01576406 | Phase I | Crizotinib | Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients | Completed | USA | 0 |
| NCT00939770 | Phase Ib/II | Crizotinib | Crizotinib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma | Completed | USA | CAN | 0 |
| 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 | USA | 2 |
| NCT03620643 | Phase II | Crizotinib Crizotinib + Fulvestrant | Crizotinib in Lobular Breast, Diffuse Gastric and Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours (ROLo) | Recruiting | 1 | |
| NCT02223819 | Phase II | Crizotinib | Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy | Active, not recruiting | USA | 0 |
| NCT04084717 | Phase II | Crizotinib | Study of Crizotinib for ROS1 and MET Activated Lung Cancer | Recruiting | CAN | 0 |
| 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 | USA | ITA | FRA | ESP | DEU | CAN | 16 |
| 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 | Active, not recruiting | USA | ITA | FRA | ESP | 5 |
| 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 | USA | 0 |
| NCT03088930 | Phase II | Crizotinib | Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer | Completed | USA | 0 |
| NCT04283669 | Phase II | Crizotinib | Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas (NF110) | Active, not recruiting | USA | 0 |
| 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 | USA | ITA | FRA | ESP | DEU | CAN | 24 |
| NCT02473497 | Expanded access | Crizotinib | Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients | Available | USA | 0 |
| 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) | Unknown status | USA | 1 |
| NCT02511184 | Phase I | Crizotinib Pembrolizumab | Crizotinib Plus Pembrolizumab In Alk-positive Advanced Non Small Cell Lung Cancer Patients | Terminated | USA | 0 |
CKB BOOST