Molecular Profile Detail

Profile Name ALK F1174V
Gene Variant Detail

ALK F1174V (gain of function - predicted)

Relevant Treatment Approaches ALK Inhibitor

Filtering

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

Sorting

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

Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK G1128S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ALK Inhibitor 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
NPM1-ALK ALK G1128S Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK G1128S in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
ALK fusion ALK S1206Y non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, an ALK S1206Y secondary mutation in the context of an ALK fusion was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer (PMID: 22277784). 22277784
ALK rearrange ALK S1206Y non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). 25724526
ALK rearrange ALK S1206Y non-small cell lung carcinoma resistant ALK Inhibitor 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
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing S1206Y in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041). 24675041
ALK neg ROS1 pos non-small cell lung carcinoma sensitive ALK Inhibitor Crizotinib Phase II Actionable In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021). detail...
ALK negative anaplastic large cell lymphoma predicted - sensitive Brentuximab vedotin Phase II Actionable In a Phase II trial (SGN-35), Adcetris (brentuximab vedotin) treatment resulted in complete remission in 57% (33/58), partial remission in 29% (17/58) of patients with relapsed or refractory systemic anaplastic large cell lymphoma, 72% (42/58) of the patients were ALK-negative (PMID: 22614995; NCT00866047). 22614995
ALK negative leukemia resistant ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative leukemia cells in culture (PMID: 22203728). 22203728
ALK negative non-small cell lung carcinoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, ALK negative non-small cell lung carcinoma cells were resistant to CEP-28122 in culture and in cell line xenograft models (PMID: 22203728). 22203728
ALK negative colon carcinoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, CEP-28122 did not inhibit tumor growth in cell line xenograft models of ALK-negative colon carcinoma (PMID: 22203728). 22203728
ALK negative lymphoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative lymphoma cells in culture (PMID: 22203728). 22203728
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor 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
NPM1-ALK ALK L1122V ALK L1196M anaplastic large cell lymphoma resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
ALK fusion ALK G1202R KIT amp non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
EML4-ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK fusion ALK G1202R non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK rearrange ALK G1202R ALK G1269A ALK L1204V non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells expressing ALK G1201R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503). 30093503 detail...
EML4-ALK ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to RXDX-101 (PMID: 26939704). 26939704
EML4-ALK ALK G1202R lung cancer conflicting ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). 26144315
EML4-ALK ALK G1202R lung cancer conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R non-small cell lung carcinoma resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041). 24675041
EML4-ALK ALK G1202R non-small cell lung carcinoma resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK G1202R non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079). 24736079
EML4-ALK ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
ALK rearrange ALK V1180L ALK L1196M ALK G1202R non-small cell lung carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). 29935304
ALK G1202R Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited ALK G1202R and suppressed tumor growth in cell line xenograft models with ALK G1202R (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
ALK rearrange ALK G1202R ALK L1196M non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4-ALK ALK F1174V ALK G1202R non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041). 24675041
ALK rearrange ALK G1202R non-small cell lung carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304). 29935304
ALK rearrange ALK G1202R non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468). 27130468
ALK rearrange ALK G1202R non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684). 28285684
ALK rearrange ALK G1202R ALK G1269A non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F non-small cell lung carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor 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
ALK rearrange ALK L1198F ALK mut non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer who acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526). 25724526
ALK rearrange ALK I1171N ALK L1198F non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). 29650534
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor decreased response ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F had reduced sensitivity to growth inhibition mediated by Lorlatinib (PF-06463922) in comparison to EML4-ALK wild type in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910). 26698910
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK1198F were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor 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
NPM1-ALK ALK F1174V ALK L1198F anaplastic large cell lymphoma resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
ALK rearrange ALK C1156Y ALK L1198F non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK E1210K non-small cell lung carcinoma predicted - resistant ALK Inhibitor 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
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with E1210K were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor 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
NPM1-ALK ALK E1210K anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK E1210K were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). 29636358
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K ALK S1206C non-small cell lung carcinoma resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358). 29636358
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK rearrange ALK E1210K ALK D1203N ALK G1269A non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK C1156Y anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK C1156Y were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
EML4-ALK ALK C1156Y ALK F1174V Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK C1156Y non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526). 25724526
EML4-ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK L1196M lung adenocarcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195). 20979473
EML4-ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y non-small cell lung carcinoma conflicting ALK Inhibitor Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) demonstrated tumor growth inhibition in xenograft models of a human non-small cell lung cancer cell line harboring EML4-ALK with ALK C1156Y when compared to Xalkori (crizotinib) (PMID: 24675041). 24675041
EML4-ALK ALK C1156Y non-small cell lung carcinoma conflicting ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation C1156Y, did not respond to Zykadia (ceritinib) therapy (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were sensitive to Entrectinib (RXDX-101), resulting in anti-proliferative activity (PMID: 26939704). 26939704
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK C1156Y in the context of EML4-ALK in culture (Cancer Res 2018;78(13 Suppl):Abstract nr 4794). detail...
EML4-ALK ALK C1156Y non-small cell lung carcinoma no benefit Luminespib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with an ALK C1156Y secondary Xalkori (crizotinib) resistance mutation did not respond to Luminespib (AUY922) therapy (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing ALK C1156Y in the context of EML4-ALK demonstrated minimal sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK C1156Y non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing EML4-ALK with ALK C1156Y were sensitive to Alecensa (alectinib) in culture (PMID: 21575866). 21575866
EML4-ALK ALK C1156Y non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer developed resistance to Xalkori (crizotinib) with the emergence of ALK C1156Y, a secondary resistance mutation (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK ALK C1156Y were insensitive to Xalkori (crizotinib) as demonstrated by lack of growth inhibition and lack of kinase inhibition in culture (PMID: 21613408). 21613408
EML4-ALK ALK C1156Y Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408). 21613408
ALK C1156Y Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical Actionable In a preclinical study, ALK C1156Y was sensitive to Alecensa (alectinib) in an in vitro enzyme assay (PMID: 21575866). 21575866
EML4-ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK I1171N non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911). 27565911
ALK rearrange ALK I1171N non-small cell lung carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304). 29935304
ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4-ALK ALK I1171N Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). 25393798
EML4-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
ALK rearrange ALK I1171N MET amp non-small cell lung carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, MET amplification was identified together with a pre-existing ALK I1171N at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange ALK I1171N ALK D1203N non-small cell lung carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
NPM1-ALK ALK I1171N anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1171N were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor 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
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
ALK wild-type TP53 P177T neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). 26438783
ALK wild-type TP53 C176F neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). 26438783
ALK wild-type TP53 mutant neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). 26438783
ALK wild-type breast cancer predicted - sensitive ALK Inhibitor Cisplatin + Dalantercept Preclinical - Cell line xenograft Actionable In a preclinical study, Dalantercept (ACE-041) in combination with Platinol (cisplatin) resulted in decreased tumor growth in cell line xenograft models of breast cancer (PMID: 26373572). 26373572
ALK wild-type melanoma sensitive ALK Inhibitor Dalantercept + Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, Dalantercept (ACE-041) in combination with Adria (doxorubicin) resulted in decreased tumor growth in cell line xenograft models of melanoma, with increased efficacy over either agent alone (PMID: 26373572). 26373572
ALK wild-type head and neck cancer predicted - sensitive ALK Inhibitor Cisplatin + Dalantercept Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Dalantercept (ACE-041) to Platinol (cisplatin) treatment resulted in increased cytoxicity and decreased tumor growth in cell line xenograft models of head and neck cancer (PMID: 26373572). 26373572
ALK wild-type neuroblastoma resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK wild-type neuroblastoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 22203728). 22203728
ALK wild-type endometrial cancer no benefit ALK Inhibitor Dalantercept Phase II Actionable In a Phase II clinical trial, treatment with Dalantercept (ACE-041) did not demonstrate activity as single agent in recurrent or persistent endometrial cancer, with a median progression-free survival (PFS) of 2.1 months, overall survival of 14.5 months, no objective responses, and stable disease in 57% (16/28) of patients (PMID: 25888978). 25888978
ALK wild-type Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing wild-type ALK in culture and suppressed tumor growth in xenograft models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
ALK wild-type TP53 wild-type neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). 26438783
ALK wild-type TP53 H168R neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). 26438783
EML4-ALK ALK L1152P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152P Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152P Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor 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
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M anaplastic large cell lymphoma resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive ALK Inhibitor 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
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK P1139S in the context of NPM1-ALK in culture (PMID: 25421750). 25421750
ALK G1123S ALK rearrange lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK G1123S ALK rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK rearrange ALK T1151dup ALK G1269A non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526). 25724526
ALK rearrange TP53 mut non-small cell lung carcinoma decreased response ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). 30165392
ALK rearrange TP53 mut non-small cell lung carcinoma decreased response ALK Inhibitor Crizotinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). 30165392
ALK rearrange TP53 mut non-small cell lung carcinoma decreased response ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). 30165392
ALK rearrange TP53 mut non-small cell lung carcinoma decreased response ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). 30165392
ALK amp ALK rearrange non-small cell lung carcinoma resistant ALK Inhibitor 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 amp ALK rearrange non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a retrospective analysis, two non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK amplification (PMID: 25724526). 25724526
ALK rearrange ALK V1180L non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK V1180L non-small cell lung carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). 29935304
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a retrospective analysis, four non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK L1196M (PMID: 25724526). 25724526
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
ALK rearrange ALK I1171T non-small cell lung carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung adenocarcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung adenocarcinoma resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange RB1 C706F TP53 loss lung small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). 28285684
ALK rearrange MAP2K1 K57N non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib + Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of AZD6244, resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). 25394791
ALK rearrange SRC pos non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib + Saracatinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Saracatinib (AZD0530) and Zykadia (ceritinib) demonstrated efficacy in non-small cell lung cancer patient derived cells harboring an ALK fusion and upregulation of SRC in culture (PMID: 25394791). 25394791
ALK rearrange ALK D1203N non-small cell lung carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange MET amp lung adenocarcinoma sensitive ALK Inhibitor 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 rearrange MET amp lung adenocarcinoma resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement developed resistance to Alecensa (alectinib) treatment, and subsequently was found to harbor amplification of MET (PMID: 24128725, PMID: 24518097). 24518097 24128725
ALK rearrange non-small cell lung carcinoma no benefit Pembrolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Phase III Actionable In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099). 28126333
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib FDA approved Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). 25754348
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Phase II Actionable In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060). 27432917
ALK rearrange non-small cell lung carcinoma no benefit Durvalumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Durvalumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Phase I Actionable In a clinical study, combined analysis of 2 Phase I trials showed Entrectinib (RXDX-101) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697). 28183697
ALK rearrange Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib + Crizotinib Clinical Study - Cohort Actionable In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). 25724526
ALK rearrange non-small cell lung carcinoma no benefit Erlotinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Phase I Actionable In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). 26966027
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 no benefit Afatinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461). 27836716
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in the guidelines as first-line and subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib FDA approved Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib FDA approved Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). 28586279
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as the preferred first-line therapy and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Phase II Actionable In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). 26598747
ALK rearrange non-small cell lung carcinoma no benefit Atezolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Atezolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer that have progressed on Xalkori (crizotinib) and Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib), or on Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib)(NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Phase II Actionable In a Phase II trial, Lorbrena (lorlatinib treatment resulted in an objective response (OR) rate of 90% (27/30; 1 complete response (CR) and 26 partial responses (PR)) and an intracranial response rate of 66.7% (2/3) in treatment-naive non-small cell lung cancer (NSCLC) patients harboring an ALK rearrangement, and an OR rate of 47% (93/198; 4 CR, 89 PR) and an objective intracranial response rate of 63% (51/81) in ALK-rearranged NCSLC patients that had received prior therapy (PMID: 30413378; NCT01970865). 30413378
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (103/215, 4% complete response, 44% partial response) in ALK-rearranged non-small cell lung carcinoma patients that had received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865). detail...
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). 29074098
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ensartinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Ensartinib (X-396), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive ALK Inhibitor Ensartinib Phase Ib/II Actionable In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months (PMID: 29563138; NCT01625234). 29563138
ALK rearrange non-small cell lung carcinoma no benefit Osimertinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Nivolumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Gefitinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK mut TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). 26438783
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L non-small cell lung carcinoma resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing ALK V1180L in the context of EML4-ALK in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK V1180L non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534). 25228534
ALK G1128A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK G1128A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK fusion Advanced Solid Tumor predicted - sensitive ALK Inhibitor Repotrectinib Phase I Actionable In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). detail...
ALK fusion anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). 28787259
ALK fusion non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Phase Ib/II Actionable In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). 24091716
ALK fusion non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Phase II Actionable In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008)) detail...
ALK fusion non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Phase III Actionable In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)). detail...
ALK fusion colorectal cancer sensitive ALK Inhibitor Entrectinib Phase I Actionable In a Phase I clinical trial, Entrectinib (RXDX-101) treatment resulted in partial response for more than 3 months in a colorectal cancer patient harboring a CAD-ALK gene fusion (PMID: 26633560). 26633560
ALK fusion inflammatory myofibroblastic tumor sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK fusion inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770). 28787259
ALK fusion inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK F1245V neuroblastoma predicted - sensitive ALK Inhibitor Entrectinib Case Reports/Case Series Actionable In a clinical study, combined analysis of 2 Phase I trials showed Entrectinib (RXDX-101) treatment to result in a partial response that lasted 8.3 months in a patient with neuroblastoma harboring ALK F1245V, who remained on treatment for over 3.5 years due to clinical benefit (PMID: 28183697). 28183697
EML4-ALK ALK F1174L ALK L1198V non-small cell lung carcinoma resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358). 29636358
ALK F1174L ALK L1198P neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
ALK F1174L ALK L1198P neuroblastoma resistant ALK Inhibitor 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
EML4-ALK ALK L1198P Advanced Solid Tumor resistant ALK Inhibitor 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 L1198P Advanced Solid Tumor resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
ALK Y1278S Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1174V neuroblastoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722). 27049722
EML4-ALK ALK F1174V ALK I1171S non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). 26464158
EML4-ALK ALK F1174V non-small cell lung carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK initially responded to Xalkori (crizotinib), but then progressed due to acquisition of the secondary resistance mutation, ALK F1174V, and then responded to treatment with Alecensa (alectinib), demonstrating a complete response in one lung nodule and a 44% decrease in size in a second lung nodule (PMID: 26464158). 26464158
EML4-ALK ALK F1174V Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK F1174V non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079). 24736079
EML4-ALK ALK F1174V Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive ALK Inhibitor 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 F1174V Advanced Solid Tumor decreased response ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical trial, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor predicted - sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical trial, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V, but to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). 25421750
ALK amp ALK F1174V neuroblastoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK amp ALK F1174V neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
EML4-ALK ALK L1196M ALK F1174V Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK R1275Q in culture (PMID: 26554404). 26554404
ALK R1275Q Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 22203728). 22203728
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783). 26438783
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and irapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). 26554404
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor decreased response ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4-ALK ALK F1174C non-small cell lung carcinoma resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041). 24675041
EML4-ALK ALK F1174C Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK F1174C ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK F1174C Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK C1156F were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor sensitive ALK Inhibitor 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
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and ALK D1203N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and ALK D1203N were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with C1156F and D1203N were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor 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 C1156F ALK D1203N anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK C1156F and D1203N were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
ALK F1174L ALK G1123D neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK G1123D in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor 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 F1174L Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L anaplastic large cell lymphoma resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK F1174L were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK amp ALK F1174L neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK amp ALK F1174L neuroblastoma sensitive ALK Inhibitor 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 TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). 26438783
EML4-ALK ALK L1196M ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). 30322862
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). 26554404
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1174L neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728). 22203728
ALK F1174L neuroblastoma resistant ALK Inhibitor Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK 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 sensitive ALK Inhibitor AZD3463 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851). 26786851
EML4-ALK ALK F1174L Advanced Solid Tumor conflicting ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK F1174L ALK G1123S neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK G1123S in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
EML4-ALK ALK F1245C non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591). 26775591
EML4-ALK ALK F1245C non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591). 26775591
ALK F1245C TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). 26438783
ALK F1245C neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C neuroblastoma resistant ALK Inhibitor Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1245C Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404). 26554404
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor 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
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1196M ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4-ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK I1179V Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A ALK L1196M non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4-ALK ALK G1269A ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response ALK Inhibitor 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
NPM1-ALK ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical trial, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32). detail...
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (Cancer Res 2018;78(13 Suppl):Abstract nr 4794). detail...
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). 26144315
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408). 21613408
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Entrectinib (RXDX-101), resulting in anti-proliferative activity in culture (PMID: 26939704). 26939704
EML4-ALK ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504). 21502504
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041). 24675041
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910) 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 26698910 27432227
EML4-ALK ALK S1206F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853). 27780853
ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910). 26698910 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) modestly inhibited growth of transformed cells expression EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines expressing ALK G1269A in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK G1269A non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated stable disease when treated with Xalkori (crizotinib), but then progressed, and was found to harbor a secondary resistance mutation, ALK G1269A (PMID: 22235099). 22235099
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315). 26144315
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of a Xalkori (crizotinib)-resistant human non-small cell lung cancer cell line harboring an EML-ALK fusion with ALK G1269A in culture and induced tumor regression in cell line xenograft models (PMID: 26849637, PMID: 23344087). 26849637 23344087
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK fusion positive non-small cell lung cancer with ALK G1269A had a partial response to Alecensa (alectinib) treatment (PMID: 26849637). 26849637
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22235099). 22235099
EML4-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A Advanced Solid Tumor decreased response ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated a decreased response when treated with Entrectinib (RXDX-101) compared to cells expressing wild-type EML4-ALK (PMID: 26939704). 26939704
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines harboring EML4-ALK with ALK G1269A demonstrated sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A anaplastic large cell lymphoma resistant ALK Inhibitor 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
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174I were resistant to ASP3026 relative to wild type NPM1-ALK in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK F1174I were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor 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 act mut TP53 wild-type neuroblastoma predicted - sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). 26438783
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Alectinib FDA approved Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in ALK-positive non-small cell lung cancer patients (PMID: 28586279; NCT02075840). 28586279
ALK positive non-small cell lung carcinoma no benefit ALK Inhibitor Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in ALK positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer patients, and as subsequent therapy in patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org). detail...
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Ceritinib FDA approved Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). 25754348
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (97/198, 4% complete response, 44% partial response) in ALK positive non-small cell lung carcinoma patients received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865). detail... detail...
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Ensartinib Phase Ib/II Actionable In a Phase Ib/II trial, Ensartinib (X-396) treatment resulted in partial response (PR) in 60% (19/30) and stable disease in 7% (2/30) of ALK positive non-small cell lung carcinoma patients, PR was 88% (7/8) in crizotinib-naïve patients and 83% (10/12) in patients with prior crizotinib treatment (J Clin Oncol 34, 2016 (suppl; abstr 9056)). detail...
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Belizatinib Phase I Actionable In a Phase I clinical trial, Belizatinib (TSR-011) treatment resulted in a partial response in 60% (3/5) of non-small cell lung cancer patients positive for Alk (J Clin Oncol 32, 2014 (suppl; abstr e19005)). detail...
ALK positive non-small cell lung carcinoma sensitive ALK Inhibitor Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in stable disease in a patient with ALK-positive non-small cell lung carcinoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)). detail...
ALK positive neuroblastoma sensitive ALK Inhibitor Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in partial response in a patient with ALK-positive neuroblastoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)). detail...
ALK positive Advanced Solid Tumor sensitive ALK Inhibitor Belizatinib Phase Ib/II Actionable In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK positive advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). detail...
EML4-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor 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 I1171S non-small cell lung carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). 25393796
EML4-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859), however, another study with comparable cells demonstrated sensitivity (PMID: 27432227). 27432227 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859), however, in another study comparable cells demonstrated sensitivity (PMID: 27432227). 27009859 27432227
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor 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 I1171S Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S anaplastic large cell lymphoma resistant ALK Inhibitor 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 I1171S Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK D1091N neuroblastoma sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851). 26786851
ALK D1091N neuroblastoma sensitive ALK Inhibitor AZD3463 + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma predicted - sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma predicted - sensitive ALK Inhibitor Alectinib + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
NPM1-ALK ALK N1178H Advanced Solid Tumor sensitive ALK Inhibitor 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
NPM1-ALK ALK N1178H Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK N1178H in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor decreased response ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK N1178H were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor 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 I1171T Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1171T were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T anaplastic large cell lymphoma resistant ALK Inhibitor 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 I1171T Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
ALK I1171T ganglioneuroblastoma predicted - sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma (PMID: 29907598). 29907598
EML4-ALK ALK I1171T Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T non-small cell lung carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534), however, another study with comparable cells demonstrated sensitivity in culture (PMID: 27432227). 25228534 27432227
EML4-ALK ALK I1171T non-small cell lung carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798). 25393798
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK amp neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 22203728). 22203728
ALK amp neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of ALK amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK amp neuroblastoma sensitive ALK Inhibitor 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
NPM1-ALK amp anaplastic large cell lymphoma resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma decreased response ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK demonstrated a decreased response compared to parental cell lines harboring NPM1-ALK when treated with Alecensa (alectinib) in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma resistant ALK Inhibitor 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
NPM1-ALK amp anaplastic large cell lymphoma resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
ALK amp Tp53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor 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 R1192P anaplastic large cell lymphoma resistant ALK Inhibitor 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
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor decreased response ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P had a reduced response to AZD3463 mediated growth inhibition in culture compared to cells expressing wild-type NPM1-ALK (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4-ALK ALK T1151dup Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK T1151dup Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK T1151dup Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853). 27780853
NPM1-ALK ALK L1196Q anaplastic large cell lymphoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK containing ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK L1196Q anaplastic large cell lymphoma sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of human anaplastic large cell lymphoma cell lines harboring NPM1-ALK containing the crizotinib-resistant mutation ALK L1196Q in culture (PMID: 25749034). 25749034
EML4-ALK ALK L1152R Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641). 21791641
EML4-ALK ALK L1152R Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152R Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK L1152R Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152R non-small cell lung carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a brief response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641). 21791641
NPM1-ALK ALK S1206C Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK and ALK S1206C were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor decreased response ALK Inhibitor 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 S1206C Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK S1206C were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK S1206C were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C anaplastic large cell lymphoma resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK ALK S1206C were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK S1206C to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
EML4-ALK ALK G1202del Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated moderate resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Alunbrig (brigatinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response ALK Inhibitor 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
Clinical Trial Phase Therapies Title Recruitment Status