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| Gene | ALK |
| Variant | fusion |
| Impact List | fusion |
| Protein Effect | unknown |
| Gene Variant Descriptions | ALK fusion indicates a fusion of the ALK gene, but the fusion partner is unknown. |
| Associated Drug Resistance | |
| Category Variants Paths |
ALK mutant ALK rearrange ALK fusion |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 | 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 | 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 fusion, and was associated with CNS disease-free survival benefit (HR 0.22) (PMID: 38598794; NCT03456076). | detail... 38598794 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 | 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 | 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 | Advanced Solid Tumor | sensitive | Entrectinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival not reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 33.3% (1/3) in patients harboring ALK fusions (PMID: 35395680; NCT02650401). | 35395680 |
| 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 - 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... 30413378 detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | 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 fusion | lung non-small cell carcinoma | sensitive | 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 fusion | inflammatory myofibroblastic tumor | sensitive | 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). | detail... 28787259 |
| ALK fusion | inflammatory myofibroblastic tumor | sensitive | 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 fusion | anaplastic large cell lymphoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). | 28787259 detail... |
| ALK fusion | Advanced Solid Tumor | predicted - sensitive | Repotrectinib | Phase I | Actionable | In a Phase I (TRIDENT-1) trial, Augtyro (repotrectinib) 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 | 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 | 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 | 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 fusion | Erdheim-Chester disease | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538). | 35373538 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538). | 35373538 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of brain metastases after 6 months in a patient with concomitant ALK fusion-positive lung adenocarcinoma and ERBB2 (HER2)-mutant, hormone receptor-negative invasive ductal carcinoma of the breast (PMID: 37113357). | 37113357 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the brain and spinal cord metastases in a patient with ALK-positive lung adenocarcinoma, who had been previously treated with Xalkori (crizotinib) (PMID: 35373538). | 35373538 |
| ALK fusion | Erdheim-Chester disease | sensitive | Alectinib | Guideline | Actionable | Alecensa (alectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| ALK fusion | Erdheim-Chester disease | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| ALK fusion | Erdheim-Chester disease | sensitive | Ceritinib | Guideline | Actionable | Zykadia (ceritinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| ALK fusion | Erdheim-Chester disease | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | TQ-B3139 | Phase I | Actionable | In a Phase I trial, TQ-B3139 (CT-711) treatment demonstrated safety and resulted in an overall response rate (ORR) of 61.9% (39/63), an intracranial ORR of 70% (7/10), disease control rate of 84.1% (53/63), and median progression-free survival (PFS) of 19.0 months in patients with non-small cell lung cancer harboring an ALK fusion or ROS1 fusion, with TKI-naive patients demonstrating a longer PFS (25.2 mo vs 5.4 mo, p=0.02) (PMID: 35940055; NCT03099330). | 35940055 |
| ALK fusion | lung non-small cell carcinoma | predicted - sensitive | APG-2449 | Phase I | Actionable | In a Phase I trial, APG-2449 treatment was well tolerated and resulted in preliminary efficacy with 4 partial responses among 14 patients with non-small cell lung cancer harboring an ALK fusion who previously progressed on a second-generation ALK inhibitor, 1 intracranial complete response and 3 partial responses among 8 patients with brain metastases, and an overall response rate of 80% and a disease control rate of 100% among 10 TKI-naive patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 9071-9071). | detail... |
| ALK fusion | anaplastic large cell lymphoma | predicted - sensitive | Crizotinib + Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Etoposide + Ifosfamide + Methotrexate | Phase II | Actionable | In a Phase II trial (ANHL12P1), the addition of Xalkori (crizotinib) to standard chemotherapy prevented disease relapse in pediatric patients with ALK fusion-positive anaplastic large cell lymphoma, with an event-free survival rate of 76.8%, a 2-year overall survival of 95.2%, and a complete response rate among evaluable patients of 91.7% (55/60) after 2 cycles and 98.3% (59/60) after 6 cycles (PMID: 36534942; NCT01979536). | 36534942 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a significant reduction of brain metastases in a patient with lung adenocarcinoma harboring an ALK fusion (PMID: 38158887). | 38158887 |
| ALK fusion | Advanced Solid Tumor | predicted - sensitive | Alectinib | Phase Ib/II | Actionable | In a Phase I/II trial, Alecensa (alectinib) treatment resulted in 1 complete response, 3 partial responses, and 2 stable diseases in 7 evaluable pediatric patients with advanced solid tumors harboring ALK fusions with TPM3, CLTC, PLEKHA7, DCTN1, or HNRNPA3 (Cancer Res (2024) 84 (7_Supplement): CT039; NCT04774718). | detail... |
| ALK fusion | renal cell carcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in a complete radiological response ongoing for at least 12 months in a patient with metastatic renal cell carcinoma harboring an ALK fusion (PMID: 39205743). | 39205743 |
| ALK fusion | lung non-small cell carcinoma | predicted - sensitive | NVL-655 | Phase I | Actionable | In a Phase I trial (ALKOVE-1), NVL-655 treatment demonstrated activity in patients with ALK-positive non-small cell lung cancer (including patients with ALK fusion with or without secondary ALK mutations), resulting in a response rate of 38% (39/103), a median duration of response (DOR) of 9.2 months, DOR greater than 6 months in 79% of patients, and a response rate of 39% (15/38) at the RP2D dose of 150mg (Ann Oncol (2024) 35 (suppl_2): S802-S803; NCT05384626). | detail... |