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Gene ETV6 ALK
Variant ETV6 - ALK
Impact List fusion
Protein Effect gain of function - predicted
Gene Variant Descriptions ETV6-ALK results from the fusion of ETV6 and ALK (PMID: 29327718), which is transforming in culture (PMID: 21572589) and therefore, is predicted to confer a gain of function. ETV6-ALK fusion has been identified in epithelioid fibrous histiocytoma (PMID: 29327718).
Associated Drug Resistance

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ETV6 - ALK Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ETV6-ALK demonstrated sensitivity to Rozlytrek (entrectinib) in culture (PMID: 26939704). 26939704
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK mutant lung non-small cell carcinoma no benefit 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 patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ETV6 mutant myelodysplastic syndrome not applicable N/A Clinical Study Prognostic In multiple clinical studies, ETV6 mutations were associated with a shorter overall survival in patients with myelodysplastic syndrome (PMID: 21714648, PMID: 21877899, PMID: 26769228). 21877899 26769228 21714648
ETV6 mutant myelodysplastic syndrome not applicable N/A Guideline Prognostic ETV6 mutations are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
ALK fusion lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378
ALK fusion anaplastic large cell lymphoma sensitive Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). 28787259
ALK fusion Advanced Solid Tumor predicted - sensitive 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 lung non-small cell carcinoma sensitive Ceritinib FDA approved - On Companion Diagnostic 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). detail... detail... 25754348
ALK fusion lung non-small cell carcinoma sensitive Alectinib FDA approved - On Companion Diagnostic 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 rearrangements (PMID: 28586279; NCT02075840). detail... 28586279 detail...
ALK fusion lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive 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 inflammatory myofibroblastic tumor sensitive Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770). 28787259
ALK fusion lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic 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 (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456 detail...
ALK fusion lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK fusion lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). 25470694 detail... detail...
ALK fusion lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK fusion (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 30715168 detail...
ALK fusion lung non-small cell carcinoma sensitive Ensartinib Phase II Actionable In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693). 31628085
ALK rearrange lung non-small cell 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 rearrange lung non-small cell carcinoma predicted - sensitive 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 with an ALK rearrangement (J Clin Oncol 32, 2014 (suppl; abstr e19005)). detail...
ALK rearrange lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). 27022118
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior (PMID: 30715168, PMID: 30285222; ESMO guidelines). 30715168 30285222 detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). detail... 25470694 detail...
ALK rearrange lung non-small cell carcinoma 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 lung non-small cell 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 lung non-squamous non-small cell carcinoma sensitive 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 Advanced Solid Tumor sensitive 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-rearranged advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at a lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). detail...
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive 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, and a response rate of 80% (12/15) in crizotinib-naïve patients and 69% (20/29) in patients with prior crizotinib treatment (PMID: 29563138; NCT01625234). 29563138
ALK rearrange lung non-small cell 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 lung non-small cell 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 lung non-small cell carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 detail... 30285222
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic 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 (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). detail... 28475456
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in 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 anaplastic large cell lymphoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 30285222 detail...
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Alectinib FDA approved - On Companion Diagnostic 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 detail... detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Prognostic The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Diagnostic ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma predicted - sensitive PLB1003 Phase I Actionable In a Phase Ia trial, PLB1003 demonstrated safety and preliminary efficacy, resulted in a disease control rate of 86% (12/14, 10 partial response, 2 stable disease) in patients with ALK-rearranged non-small cell lung cancer who progressed on or did not tolerate previous treatment (Journal of Thoracic Oncology, Volume 14, Issue 10, S651). detail...
ALK rearrange lung non-small cell carcinoma no benefit 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 patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK rearrange Advanced Solid Tumor sensitive 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 lung non-small cell carcinoma sensitive Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 detail... 30285222
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Ceritinib FDA approved - On Companion Diagnostic 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 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on a second-generation ALK tyrosine kinase inhibitor (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 detail... 30715168
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer 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 lung non-small cell carcinoma sensitive 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 inflammatory myofibroblastic tumor sensitive Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell 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 Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a Phase I trial, Rozlytrek (entrectinib) 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 Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) 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
Molecular Profile Protein Effect Treatment Approaches
ETV6 - ALK gain of function - predicted ALK Inhibitor