Therapy Detail

Therapy Name Crizotinib
Synonym
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 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 20 MET Inhibitor 51 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 non-small cell lung cancer (FDA.gov).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET N375S oral cavity cancer no benefit Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with oral cavity cancer harboring MET N375S demonstrated progressive disease and overall survival of five weeks when treated with Xalkori (crizotinib) (PMID: 28514312). 28514312
EML4-ALK ALK F1174V non-small cell lung 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
ALK rearrange MET amp lung adenocarcinoma sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement who developed resistance to Alecensa (alectinib) likely due to acquisition of MET amplification, responded well to treatment with Xalkori (crizotinib), demonstrating a radiological response after 12 days (PMID: 24128725, PMID: 24518097). 24128725 24518097
ALK amp ALK F1174L 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 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
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 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
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
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
MET amp TP53 del breast cancer sensitive Crizotinib Preclinical Actionable In a preclinical study, Xalkori (crizotinib) treatment resulted in complete tumor regression in transplant models of TP53-null-luminal breast cancer harboring MET amplification (PMID: 27149990). 27149990
ALK rearrange ALK T1151dup ALK G1269A non-small cell lung carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526). 25724526
ALK rearrange ALK S1206Y non-small cell lung carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). 25724526
ALK rearrange ALK S1206Y non-small cell lung 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
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 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
KRAS G12D MET over exp stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human gastric cancer cell line with high levels of MET expression and expressing KRAS G12D was resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26432108). 26432108
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
ALK neg ROS1 pos non-small cell lung 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 positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021). detail...
MET over exp MET Y1230C MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, acquired MET Y1230C and MET Y1230H mutations were associated with secondary resistance to Xalkori (crizotinib) in a MET-over expressing gastric cancer cell line xenograft model, and cells derived from this model demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21266357). 21266357
MET M1149T papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET M1149T demonstrated stable disease when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
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 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 HRAS amp non-small cell lung 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
KRAS over exp MET del exon14 stomach cancer predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, gastric cancer cells harboring a MET exon 14 splice site mutation demonstrated some resistance to treatment with Xalkori (crizotinib) when overexpressing wild-type Kras in culture (PMID: 30072474). 30072474
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 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
MET del exon14 MET D1228N lung squamous cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with squamous cell lung cancer harboring a MET exon 14 skipping mutation was determined to have acquired MET D1228N after progression on Xalkori (crizotinib) therapy (PMID: 27343442). 27343442
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
EML4-ALK KRAS G12C non-small cell lung carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and KRAS G12C demonstrated a minimal response when treated with Xalkori (crizotinib), and eventually progressed (PMID: 29636358). 29636358
MET R988C Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing MET R998C demonstrated sensitivity to Xalkori (crizotinib) in culture (PMID: 17483355). 17483355
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
MET amp MET del exon14 lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient co-harboring MET exon 14 deletion and MET amp was sensitive to Xalkori (crizotinib), demonstrating a partial response for 8 months (PMID: 28765324). 28765324
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 ALK L1152R non-small cell lung 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
MET amp MET D1228N triple-receptor negative breast cancer predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, MET D1228N was identified as an acquired mutation at disease progression in a patient with triple-receptor negative breast cancer harboring a 30-fold amplification of MET, after initial response to Xalkori (crizotinib) treatment (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1317). detail...
MET F1200I papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET G1163T demonstrated a partial response with a duration of 37.3 months when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
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 in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
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
EML4-ALK ALK C1156Y non-small cell lung 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
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring MET deletion exon 14 responded to Xalkori (crizotinib), demonstrating a near complete response at 3 months, however, after 9 months progression ensued and a re-biospy identified MET del exon14, MET amplification, MET D1228N, MET Y1230H, MET Y1230S, and MET G1163R (PMID: 28522754). 28522754
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring MET deletion exon 14 and MET amplification demonstrated resistance to Xalkori (crizotinib), and the patient was found to have acquired MET Y1230H, MET D1228N, MET Y1230S, and MET G1163R (PMID: 28765324). 28765324
EML4-ALK ALK D1203N ALK F1174C 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
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 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
EML4-ALK GNAS amp non-small cell lung 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
MET D1228N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were resistant to treatment with Xalkori (crizotinib), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in mouse models (PMID: 28396313). 28396313
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
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
MET Y1230C stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a Capmatinib (INC280)-resistant gastric cancer cell line (PMID: 15494073) harboring MET Y1230C also demonstrated resistance when treated with Xalkori (crizotinib) (PMID: 28765324). 15494073 28765324
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
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
MET T1010I lung carcinoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, lung carcinoma cell lines harboring MET T1010I showed sensitivity to Xalkori (crizotinib) in cell culture (PMID: 17483355). 17483355
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...
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
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
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
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
MET F1200L MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Xalkori (crizotinib) in culture for several months developed resistance and was found to co-harbor MET Y1230H and MET F1200L(PMID: 28765324). 28765324 15494073
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 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
MET del exon14 Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a deletion of MET exon 14 were sensitive to Xalkori (crizotinib) treatment in culture, demonstrating inhibition of spheroid growth (PMID: 28765324). 28765324
MET del exon14 lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical study, three patients with lung adenocarcinoma harboring a MET exon 14 skipping mutation demonstrated partial responses when treated with Xalkori (crizotinib) (PMID: 25971939). 25971939
ERBB2 amp MET amp esophageal carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human esophageal carcinoma cell line harboring amplification of ERBB2 (HER2) and MET was resistant to Xalkori (crizotinib) in culture (PMID: 26432108). 26432108
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 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 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 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
ROS1 fusion KDR amp KIT amp PDGFRA amp non-small cell lung 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
EML4-ALK ALK G1269A non-small cell lung 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 non-small cell lung 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
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
ROS1 rearrange non-small cell lung 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 non-small cell lung carcinoma sensitive Crizotinib FDA approved Actionable In a Phase I trial that supported FDA approval, non-small cell lung cancer patients with ROS1 rearrangements treated with Xalkori (crizotinib) demonstrated 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 (PMID: 25264305; NCT00585195). 25264305
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
ALK rearrange ALK C1156Y non-small cell lung 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
NPM1-ALK 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
ALK amp ALK rearrange non-small cell lung 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 non-small cell lung 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 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
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
MET exon 14 non-small cell lung carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for non-small cell lung cancer patients with MET exon 14 mutations (NCCN.org). detail...
MET amp triple-receptor negative breast cancer predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a completed response that sustained for 22 weeks in a patient with triple-receptor negative breast cancer harboring a 30-fold amplification of MET, with MET overexpression and hyperactivity confirmed by IHC (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1317). detail...
Unknown unknown alveolar soft part sarcoma predicted - sensitive 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 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
ROS1 fusion ERBB2 amp FGFR3 amp RET amp non-small cell lung 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
ALK rearrange non-small cell lung 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 non-small cell lung carcinoma sensitive Crizotinib FDA approved 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
ALK rearrange non-small cell lung 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 non-small cell lung 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...
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
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 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 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 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
MET del exon14 colorectal cancer sensitive Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of patient-derived colorectal cancer cells harboring a MET exon 14 skipping mutation in culture (PMID: 26375439). 26375439
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 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
EML4-ALK ALK C1156Y ALK L1198F non-small cell lung 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 I1171T non-small cell lung 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 ALK L1196M non-small cell lung carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
ALK rearrange ALK L1196M non-small cell lung 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
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
MET amp non-small cell lung carcinoma sensitive Crizotinib Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) inhibited tumor grow in patient-derived xenograft models of MET amplified non-small cell lung cancer (PMID: 26483207). 26483207
MET amp non-small cell lung carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for non-small cell lung cancer patients with high level MET amplification (NCCN.org). detail...
ALK fusion 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 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
MET Y1230H Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Xalkori (crizotinib), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in cell line xenograft mouse models (PMID: 28396313). 28396313
KRAS mutant acute myeloid leukemia predicted - resistant Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, KRAS mutations correlated with resistance to Xalkori (crizotinib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 fusion ALK G1202R KIT amp non-small cell lung 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 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 KRAS G13D non-small cell lung carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK eventually progressed while on treatment with Xalkori (crizotinib) and was subsequently found to harbor a presumed resistance mutation, KRAS G13D (PMID: 29636358). 29636358
KRAS G12V MET amp carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with a carcinoma of unknown primary harboring MET amplification and KRAS G12V demonstrated a durable response following treatment with Xalkori (crizotinib) (PMID: 25232318). 25232318
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 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
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
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 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
EML4-ALK ALK G1269A ALK L1196M non-small cell lung 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 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
MET del exon14 stomach carcinoma sensitive Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of patient-derived gastric carcinoma cells harboring a MET exon 14 skipping mutation in culture (PMID: 26375439). 26375439
MET act mut non-small cell lung carcinoma predicted - sensitive Crizotinib Phase I Actionable In a Phase I clinical trial, Xalkori (crizotinib) was generally well-tolerated and demonstrated preliminary efficacy in patients with non-small cell lung cancer harboring MET exon 14 alterations, with anti-tumor activity demonstrated in 10/15 evaluable patients (J Clin Oncol 34, 2016 (suppl; abstr 108)). detail...
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
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
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
MET positive clear cell sarcoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial (CREATE), Xalkori (crizotinib) treatment in MET-positive clear cell sarcoma patients resulted in an objective response rate of 3.8% (1/26) and a median progression-free survival of 131 days, similar to results achieved with first-line Adriamycin (doxorubicin) in non-selected metastatic soft tissue sarcomas (PMID: 28950372; NCT01524926). 28950372
MET D1228H papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET D1228H demonstrated a partial response with a duration of 21.8 months when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
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
ALK rearrange TP53 mut non-small cell lung 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
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, 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
KRAS amp MET del exon14 non-small cell lung carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring a MET exon 14 splice site mutation demonstrated an initial response to Xalkori (crizotinib) for 4 months, but then developed resistance, and was found to have acquired KRAS amplification, which was also confirmed in patient-derived cells in culture (PMID: 30072474). 30072474
KIT D816G ROS1 fusion non-small cell lung 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
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
EML4-ALK ALK F1245C non-small cell lung 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 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
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
ALK amp ALK F1174V 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
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp non-small cell lung 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 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
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
MET amp liver cancer sensitive Crizotinib Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) inhibited tumor grow in patient-derived xenograft models of MET amplified liver cancer (PMID: 26483207). 26483207
EML4-ALK ALK V1180L non-small cell lung 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 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 non-small cell lung 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
EML4-ALK non-small cell lung 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
ALK fusion ALK S1206Y non-small cell lung 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
MET over exp stomach cancer sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of a human gastric cancer cell line with high levels of MET expression in culture (PMID: 26432108). 26432108
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
MET D1228V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V demonstrated resistance to treatment with Xalkori (crizotinib) in culture, resulting in sustained Met phosphorylation (PMID: 27694386). 27694386
MET del exon14 TP53 R175H histiocytic and dendritic cell cancer predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a decrease in tumor volume by more than 60% in a patient with histiocytic sarcoma harboring MET exon 14 skipping and TP53 R175H (PMID: 25971938). 25971938
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
ALK rearrange ALK E1210K non-small cell lung 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 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 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
ROS1 fusion ROS1 L2026M ROS1 L1951R non-small cell lung 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 E1210K non-small cell lung 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
Clinical Trial Phase Therapies Title Recruitment Status
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
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
NCT02075840 Phase III Alectinib Crizotinib ALEX Study: A Randomized, Phase III Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Active, not 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
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 Dasatinib Mitoxantrone Vinblastine Cytarabine Tretinoin Clofarabine Teniposide Docetaxel Pazopanib Oxaliplatin Streptozocin Paclitaxel Bendamustine Mechlorethamine Mitotane Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma Recruiting
NCT03052608 Phase III Lorlatinib Crizotinib A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC Recruiting
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
NCT03737994 Phase II Cisplatin + Lorlatinib Carboplatin + Lorlatinib Ceritinib Alectinib + Cisplatin Alectinib + Carboplatin Ceritinib + Cisplatin Pemetrexed Carboplatin + Ceritinib Cisplatin + Ensartinib Carboplatin + Ensartinib Brigatinib + Cisplatin Brigatinib Alectinib Brigatinib + Carboplatin Ensartinib Cisplatin + Pemetrexed Crizotinib Carboplatin + Pemetrexed 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
NCT01121588 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
NCT02612194 Phase II Crizotinib LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer Recruiting
NCT02693535 Phase II Cobimetinib + Vemurafenib Regorafenib Pembrolizumab Temsirolimus Dasatinib Pertuzumab + Trastuzumab Ipilimumab + Nivolumab Crizotinib Palbociclib Sunitinib Olaparib Cetuximab 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
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
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
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
NCT02511184 Phase I Crizotinib Pembrolizumab Crizotinib Plus Pembrolizumab In Alk-positive Advanced Non Small Cell Lung Cancer Patients Terminated
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
NCT02737501 Phase III Brigatinib Crizotinib ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in ALK-positive Advanced Non-Small Cell Lung Cancer Patients Active, not recruiting
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
NCT00939770 Phase Ib/II Crizotinib Crizotinib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma Completed
NCT03088930 Phase II Crizotinib Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer 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
NCT02223819 Phase II Crizotinib Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy Active, not recruiting
NCT01531361 Phase I Crizotinib Sorafenib + Vemurafenib Sorafenib or Crizotinib and Vemurafenib in Advanced Cancer Active, not recruiting
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
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 Recruiting
NCT02767804 Phase III Crizotinib Ensartinib eXalt3: Study Comparing X-396 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients Active, not recruiting
NCT03126916 Phase III Doxorubicin 131I-MIBG Sargramostim Etoposide Melphalan Busulfan Isotretinoin Vincristine 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
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
NCT02473497 Expanded access Crizotinib Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients Available
NCT01576406 Phase I Crizotinib Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients Completed
NCT01606878 Phase I Dexamethasone + Doxorubicin + Vincristine Cyclophosphamide + Topotecan Crizotinib Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma Completed