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Profile Name ALK rearrange
Gene Variant Detail

ALK rearrange (unknown)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell 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 lung non-small cell carcinoma no benefit ALK Inhibitor Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
ALK rearrange lung non-small cell 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 lung non-small cell 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 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 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 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 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 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-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 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 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). detail... 25470694 detail...
ALK rearrange lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as 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 ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell 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 lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as preferred 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 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 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 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 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 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-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 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 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 lung non-small cell 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, 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 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 lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic 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... detail... 30413378
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy 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 ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org). detail... 30285222
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) (PMID: 30285222; ESMO.org). 30285222 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org). detail... 30285222
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org). 30285222 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor 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 an ALK tyrosine kinase inhibitor (PMID: 30285222; ESMO.org). 30285222 detail...
ALK rearrange lung non-squamous non-small cell 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 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 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 lung non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 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 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 anaplastic large cell lymphoma sensitive ALK Inhibitor 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 inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor 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 adenocarcinoma predicted - sensitive ALK Inhibitor Conteltinib Phase I Actionable In a Phase I trial, Conteltinib (CT-707) demonstrated safety and preliminary efficacy, resulting in an overall response rate of 77% (10/13, 1 complete response, 9 partial responses) and a disease control rate of 85% (11/13) in patients with ALK-rearranged lung adenocarcinoma (n=12) or malignant pleural mesothelioma (n=1), median progression-free survival was 13 months in patients with lung adenocarcinoma (PMID: 32181989). 32181989
ALK rearrange malignant pleural mesothelioma no benefit ALK Inhibitor Conteltinib Case Reports/Case Series Actionable In a Phase I trial, Conteltinib (CT-707) treatment resulted in disease progression after 1 cycle in a patient with ALK-rearranged malignant pleural mesothelioma (PMID: 32181989). 32181989
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib FDA approved Actionable In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). 28787259 detail...
ALK rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Bevacizumab + Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient with brain metastasis harboring an ALK rearrangement, who had progressed on single agent Lorbrena (lorlatinib) treatment, demonstrated a partial response when treated with a combination of Lorbrena (lorlatinib) and Avastin (bevacizumab), with a 68% decrease in tumor size in the brain and a total duration of disease control for 9.1 months (PMID: 33283131). 33283131
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608). 33207094 detail... detail...
ALK rearrange lung non-small cell carcinoma no benefit Ipilimumab + Nivolumab Guideline Actionable Immune checkpoint inhibitors including Keytruda (pembrolizumab), Tecentriq (atezolizumab), and the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) are not indicated for use as initial systemic therapy in non-small cell lung cancer patients harboring oncogenes, including ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Phase III Actionable In a Phase III trial, Ensartinib (X-396) treatment significantly improved progression-free survival in patients with ALK-positive non-small cell lung cancer (25.8 vs 12.7 mo, HR 0.51, p<0.001) compared to Xalkori (crizotinib), and resulted in an intracranial response rate of 63.6% (7 of 11) in patients with target brain metastases at baselinewith compared to 21.1% (4 of 19) with Xalkori (crizotinib) (PMID: 34473194; NCT02767804). 34473194
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Ceritinib Phase I Actionable In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 75% (6/8; 2 complete responses, 4 partial responses) and a disease control rate of 88% (7/8) in pediatric patients with anaplastic large cell lymphoma harboring ALK rearrangement, with median progression-free survival not reached (PMID: 34780709; NCT01742286). 34780709
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Ceritinib Phase I Actionable In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival not reached (PMID: 34780709; NCT01742286). 34780709
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Guideline Actionable Ensartinib (X-396) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222, Version Update 15 Sept 2020; ESMO.org). detail... 30285222
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) 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 ALK Inhibitor Iruplinalkib Phase I Actionable In a Phase I trial, Iruplinalkib (WX-0593) demonstrated safety and resulted in an objective response rate (ORR) of 56.6% (56/99; all partial responses) and a disease control rate (DCR) of 83.8% (83/99), and median duration of response and median progression-free survival were not reached in non-small cell lung cancer patients with an ALK or ROS1-rearrangement, with an ORR of 58.2% (53/91; all partial responses) and DCR of 85.7% (78/91) in patients with an ALK rearrangement (PMID: 35087031; NCT03389815). 35087031
ALK rearrange epithelioid inflammatory myofibroblastic sarcoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange lung small cell carcinoma predicted - sensitive ALK Inhibitor Alectinib + Irinotecan Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Alecensa (alectinib) and Camptosar (irinotecan) resulted in a partial response with progression-free survival lasting longer than 6 months in a small cell lung carcinoma patient harboring an ALK rearrangement (PMID: 34729013). 34729013
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ceritinib + Ribociclib Phase Ib/II Actionable In a Phase I/II trial, Zykadia (ceritinib) and Kisqali (ribociclib) combination therapy demonstrated a manageable safety profile and resulted in an overall response rate of 37.0% (10/27; 1 complete response and 9 partial responses) with a median progression-free survival of 21.5 months in patients with advanced ALK-rearranged non-small cell lung cancer (PMID: 35298959). 35298959
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase II Actionable In a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an intracranial disease control rate of 95% (21/22), intracranial objective response rate of 59% (13/22; 6 complete responses, 7 partial responses), a median intracranial progression-free survival (PFS) rate of 24.6 months, and a 12-month PFS rate of 79% in patients with ALK-rearranged non-small cell lung cancer, who previously demonstrated central nervous system progression on second-generation ALK inhibitors (PMID: 35584349; NCT02927340). 35584349
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements (PMID: 30596843; ESMO.org). detail... 30596843
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements, including patients with CNS involvement, and as subsequent therapy for patients that progress on Xalkori (crizotinib) (PMID: 30596843; ESMO.org). detail... 30596843
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements, including patients with CNS involvement, and as subsequent therapy for patients that progress on Xalkori (crizotinib) (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib FDA approved Actionable In a Phase I/II trial (Study ADVL0912) that supported FDA approval, Xalkori (crizotinib) therapy was safe and resulted in an objective response rate of 86% (12/14, 5 complete responses, 7 partial responses) and stable disease in 14% (2/14) of pediatric patients with ALK-positive unresectable inflammatory myofibroblastic tumors, with a median duration of response of 1.63 years (PMID: 28787259; NCT00939770). 28787259 detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib FDA approved Actionable In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770). 29352732 detail...
ALK rearrange colon mucinous adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with colon mucinous carcinoma harboring ALK rearrangement with a response duration of 103.3 weeks (PMID: 29352732; NCT00939770). 29352732
ALK rearrange medullary thyroid carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with medullary thyroid carcinoma harboring ALK rearrangement with a response duration of 16.1 weeks (PMID: 29352732; NCT00939770). 29352732
ALK rearrange lymphoma predicted - sensitive ALK Inhibitor Crizotinib Phase I Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) treatment resulted in an objective response rate of 52.9% (9/17, 8 complete responses, 1 partial response) and stable disease in 17.6% (3/17) of patients with advanced ALK-positive lymphomas, with a median duration of response of 135.9 weeks in (PMID: 29352732; NCT00939770). 29352732
ALK rearrange lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Foritinib Phase Ib/II Actionable In a Phase I/II trial, Foritinib was well tolerated in ALK-positive non-small cell lung cancer patients, and resulted in a disease control rate (DCR) of 100% and median progression-free survival (PFS) of 33.1 mo in ALK inhibitor (ALKi)-naive and 22.1 mo in ALKi-pretreated patients in Phase I, and a DCR of 98.1% and 88.5%, and objective response rate of 92.3% and 65.4%, in ALKi-naive or crizotinib-pretreated patients, respectively, in Phase II (J Clin Oncol 40, 2022 (suppl 16; abs 9076); NCT04237805). detail...
ALK rearrange Advanced Solid Tumor predicted - sensitive ALK Inhibitor TQ-B3101 Phase I Actionable In a Phase I trial, TQ-B3101 treatment was well tolerated and resulted in an objective response rate (ORR) of 62.5% (15/24) in patients with ALK-positive, ROS1-positive, or MET-amplified advanced solid tumors, with an ORR of 62.5% (5/8) in patients with brain metastases (J Clin Oncol 38, 2020 (suppl 15; abstr e21705); NCT03019276). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Phase II Actionable In a Phase II trial (ASCEND-7), Zykadia (ceritinib) demonstrated efficacy in ALK-positive non-small cell lung cancer patients with active brain metastasis, resulting in whole-body overall response rate (ORR) of 35.7% (15/42), 30.0% (12/40), 50.0% (6/12), and 59.1% (26/44) in those who received prior radiation/ALK inhibitor (ALKi), ALKi only, radiation only, no prior radiation/ALKi, respectively, and whole-body ORR of 16.7% (3/18) in patients with leptomeningeal carcinomatosis (PMID: 35091443; NCT02336451). 35091443
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Conteltinib Phase I Actionable In a Phase I trial, Conteltinib (CT-707) demonstrated safety and efficacy in patients with ALK-positive non-small cell lung cancer, resulting in an overall response rate (ORR) of 53.3% (32/60), a disease control rate (DCR) of 80%, and a median progression-free survival of 9.26 months, with an ORR of 61.4% (25/39) and a DCR of 82.1% in ALK inhibitor-naive patients and an ORR of 33.3% (7/21) and a DCR of 76.2% (16/21) in patients previously treated with Xalkori (crizotinib) (PMID: 36424628; NCT02695550). 36424628
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response after 6 months and a complete response in the second year of treatment in an 8-year-old pediatric patient with metastatic inflammatory myofibroblastic tumor harboring an ALK rearrangement, with response ongoing after 5 years of treatment (PMID: 31615346). 31615346
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Iruplinalkib Phase II Actionable In a Phase II trial (INTELLECT), Iruplinalkib (WX-0593) treatment resulted in an IRC-assessed objective response rate (ORR) of 69.9% (102/146), investigator-assessed ORR of 63.0%, disease control rate of 94.5%, and median progression-free survival of 14.5 months in patients with ALK-positive, Crizotinib-resistant non-small cell lung cancer, and an intracranial ORR of 46% (41/90) and 64% (27/42) for patients with CNS metastases or measurable intracranial lesions, respectively (PMID: 36829154; NCT04641754). 36829154
ALK rearrange Cancer of Unknown Primary sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). detail... 30285222 36563965
ALK rearrange Cancer of Unknown Primary sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). detail... 30285222 36563965
ALK rearrange Cancer of Unknown Primary sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). detail... 30285222 36563965
ALK rearrange Cancer of Unknown Primary sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). 30285222 detail... 36563965
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Clinical Study Actionable In a clinical study, Xalkori (crizotinib) treatment resulted in an objective response rate of 59.3% (48/81, 8 complete responses), clinical benefit rate of 86.4% (70/81), median duration of response of 13.5 months, median progression-free survival of 15.8 months, and median overall survival of 46.5 months in patients with non-small cell lung cancer harboring an ALK rearrangement (PMID: 36162227; NCT02679170). 36162227
ALK rearrange Advanced Solid Tumor predicted - sensitive ALK Inhibitor Entrectinib Clinical Study Actionable In a combined analysis of 2 Phase I trials (ALKA-372-001, STARTRK-1), 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; NCT02097810). 28183697
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in disease stability in an HIV-positive pregnant patient with non-small cell lung cancer harboring an ALK translocation, with normal fetal development observed (PMID: 36644155). 36644155
ALK rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response in a pregnant patient with ALK-rearranged metastatic lung adenocarcinoma, with normal fetal development and infant development for at least the first 20 months post birth (PMID: 33795207). 33795207
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase Ib/II Actionable In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate (ORR) of 82.4% (14/17, all partial responses (PR)) and 63.6% (21/33, all PR) in Asian and non-Asian patients with ALK-positive non-small cell lung cancer who had prior Xalkori (crizotinib) treatment and an ORR of 47.2% (25/53, 2 complete responses, 23 PR) and 30.1% (22/73, all PR) in patients previously treated with any second-generation ALK inhibitor (PMID: 35660971; NCT01970865). 35660971
ALK rearrange large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 9 months in a patient with metastatic large-cell neuroendocrine carcinoma of the lung harboring an ALK rearrangement (PMID: 37456922). 37456922
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor TQ-B3139 Phase III Actionable In a Phase III trial, TQ-B3139 (CT-711) improved median progression-free survival (24.87 vs 11.60 mo; HR=0.47, p<0.0001), objective response rate (ORR) (81.68% vs 70.68%, p=0.056), and median duration of response (DOR) (25.79 vs 11.14 mo; HR=0.50, p=0.0003) compared to Xalkori (crizotinib) in ALK-rearranged non-small cell lung cancer patients, and also improved CNS ORR (78.95% vs 23.81%) and CNS DOR (25.82 vs 7.39 mo, p=0.0030) in patients with baseline brain lesions (PMID: 37574511; NCT04009317). 37574511
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Iruplinalkib Phase III Actionable In a Phase III trial (INSPIRE), Iruplinalkib (WX-0593) treatment in ALK-positive non-small cell lung cancer patients resulted in a significantly improved median progression free survival (mPFS) of 27.7 months, improved objective response rate (ORR) of 93.0% (133/143), and intracranial ORR of 90.9% (10/11) compared to a mPFS of 14.6 months (HR=0.34, p<0.0001), ORR of 89.3% (133/149), and intracranial ORR of 60.0% (9/15) with Xalkori (crizotinib) treatment (PMID: 38280448; NCT04632758). 38280448
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as initial, 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 ALK Inhibitor Ficonalkib Phase Ib/II Actionable In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 months, and an intracranial ORR of 37.5% (12/32, 4 complete responses, 8 PR) and intracranial DCR of 100% (32/32) in Chinese patients with ALK-positive non-small cell lung cancer (PMID: 38295954; NCT05257512). 38295954
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial supporting FDA approval (ALINA), adjuvant Alecensa (alectinib) treatment improved 2-year disease-free survival rate (93.8% vs 63.0%, HR 0.24, p<0.001) compared to chemotherapy in patients with resected non-small cell lung cancer harboring ALK rearrangement, and was associated with CNS disease-free survival benefit (HR 0.22) (PMID: 38598794; NCT03456076). 38598794 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase III Actionable In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608). 38819031
ALK rearrange renal cell carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with metastatic renal cell carcinoma harboring an ALK rearrangement (PMID: 33457258). 33457258
ALK rearrange large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with regression of lesions, including metastatic brain lesions, in a patient with large cell neuroendocrine carcinoma of the lung harboring an ALK rearrangement (PMID: 33352665). 33352665