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| Profile Name | ALK fusion |
| Gene Variant Detail | |
| Relevant Treatment Approaches | ALK Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| ALK fusion | anaplastic large cell lymphoma | sensitive | ALK Inhibitor | Crizotinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). | 28787259 |
| ALK fusion | 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). | detail... detail... 25754348 |
| ALK fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | Lorlatinib | FDA approved | Actionable | In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (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 | lung non-small cell carcinoma | sensitive | ALK Inhibitor | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). | detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | Brigatinib | Phase Ib/II | Actionable | In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). | 24091716 |
| ALK fusion | 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). | 28475456 detail... |
| ALK fusion | 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 fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | 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 | Advanced Solid Tumor | predicted - sensitive | ALK Inhibitor | Repotrectinib | Phase I | Actionable | In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). | detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | Alectinib | Phase II | Actionable | In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008)) | detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | Alectinib | Phase III | Actionable | In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)). | detail... |
| ALK fusion | 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 rearrangements (PMID: 28586279; NCT02075840). | detail... 28586279 detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | ALK Inhibitor | 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 | 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). | 25470694 detail... detail... |
| ALK fusion | inflammatory myofibroblastic tumor | sensitive | ALK Inhibitor | Crizotinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770). | 28787259 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT03191786 | Phase III | Atezolizumab Gemcitabine Vinorelbine | A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naive Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy (IPSOS) | Active, not recruiting |
| NCT02134886 | Phase I | Erlotinib | Erlotinib Hydrochloride in Treating Non-Small Cell Lung Cancer That is Metastatic or Cannot be Removed by Surgery in Patients With HIV Infection | Terminated |
| NCT04471428 | Phase III | Docetaxel Atezolizumab + Cabozantinib | Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy (CONTACT-01) | Recruiting |
| NCT04267237 | Phase II | Atezolizumab + RO7198457 Atezolizumab | A Study of the Efficacy and Safety of RO7198457 in Combination With Atezolizumab Versus Atezolizumab Alone Following Adjuvant Platinum-Doublet Chemotherapy in Participants Who Are ctDNA Positive After Surgical Resection of Stage II-III Non-Small Cell Lung Cancer | Recruiting |
| NCT03775486 | Phase II | Durvalumab + Olaparib Cisplatin + Durvalumab + Pemetrexed Disodium Durvalumab Carboplatin + Durvalumab + Gemcitabine Carboplatin + Durvalumab + Pemetrexed Disodium Carboplatin + Durvalumab + Nab-paclitaxel Cisplatin + Durvalumab + Gemcitabine | Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION) (ORION) | Active, not recruiting |
| NCT04467801 | Phase II | Ipatasertib Docetaxel + Ipatasertib | Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy | Not yet recruiting |
| NCT03999710 | Phase II | Durvalumab | Determining Whether Durvalumab in Combination With Radiation Therapy Can Prevent the Progression of Non-Small Cell Lung Cancer | Recruiting |
| NCT03164616 | Phase III | Durvalumab + Tremelimumab Cisplatin + Pemetrexed Disodium Carboplatin + Pemetrexed Disodium Cisplatin + Gemcitabine Carboplatin + Gemcitabine Durvalumab Carboplatin + Nab-paclitaxel | Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). (POSEIDON) | Active, not recruiting |
| NCT04005144 | Phase I | Binimetinib + Brigatinib | Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer | Recruiting |
| NCT03155620 | Phase II | Tazemetostat Larotrectinib LY3023414 Vemurafenib Palbociclib Olaparib Ulixertinib Erdafitinib Selumetinib Ensartinib | Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) | Recruiting |
| NCT04083976 | Phase II | Erdafitinib | A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations | Recruiting |
| NCT04294810 | Phase III | Atezolizumab Atezolizumab + MTIG7192A | A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer (SKYSCRAPER-01) | Recruiting |
| NCT03915951 | Phase II | Binimetinib + Encorafenib | An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer | Recruiting |
| NCT03993873 | Phase I | TPX-0022 | Phase 1 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET | Recruiting |
| NCT02587650 | Phase II | Ceritinib Capmatinib Regorafenib Entrectinib | Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma | Terminated |
| NCT03868423 | Phase II | Brigatinib | Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers | Recruiting |
| NCT03107988 | Phase I | Cyclophosphamide + Lorlatinib + Topotecan Lorlatinib | NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) | Recruiting |
| NCT03639714 | Phase Ib/II | GRT-C901 + GRT-R902 + Ipilimumab + Nivolumab | A Study of a Personalized Neoantigen Cancer Vaccine | Recruiting |
| NCT03420508 | Phase II | Ensartinib | Treating Patients With Melanoma and ALK Alterations With Ensartinib | Active, not recruiting |
| NCT03255083 | Phase I | DS-1205c + Osimertinib | DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer | Active, not recruiting |
| NCT03755102 | Phase I | Dacomitinib | A Study of Dacomitinib in Patients With Metastatic EGFR Mutant Lung Cancer Previously Treated With Osimertinib | Recruiting |
| NCT03066661 | Expanded access | Entrectinib | Expanded Access to Entrectinib for Cancers With NTRK1/2/3, ROS1, or ALK Gene Fusions | No longer available |
| NCT02154490 | Phase II | Docetaxel Nivolumab Palbociclib Durvalumab Ipilimumab + Nivolumab AZD4547 Taselisib Durvalumab + Tremelimumab Erlotinib + Rilotumumab Talazoparib Erlotinib | Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer | Active, not recruiting |
| NCT04094610 | Phase Ib/II | Repotrectinib | A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations | Recruiting |
| NCT04211337 | Phase III | Vandetanib Cabozantinib Selpercatinib | A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) | Recruiting |
| NCT02650401 | Phase I | Entrectinib | Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (STARTRK-NG) | Recruiting |
| NCT02097810 | Phase I | Entrectinib | Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations. (STARTRK-1) | Active, not recruiting |
| NCT03334617 | Phase II | AZD9150 + Durvalumab Durvalumab + Olaparib Cediranib + Durvalumab Durvalumab + Vistusertib Durvalumab + Trastuzumab deruxtecan AZD6738 + Durvalumab | Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON) | Recruiting |
| NCT02693535 | Phase II | Cobimetinib + Vemurafenib Regorafenib Ipilimumab + Nivolumab Palbociclib Afatinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer | Recruiting |
| NCT03563716 | Phase II | Atezolizumab + MTIG7192A Atezolizumab | A Study of MTIG7192A in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer | Active, not recruiting |
| NCT00932451 | Phase II | Crizotinib | An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene | Completed |
| NCT03037385 | Phase Ib/II | BLU-667 | Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (ARROW) | Recruiting |
| NCT03166631 | Phase I | BI 754091 + BI 891065 BI 891065 | A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread | Recruiting |
| NCT03213652 | Phase II | Ensartinib | Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial) | Recruiting |
| NCT03057106 | Phase II | Cisplatin Gemcitabine Carboplatin Durvalumab + Tremelimumab Pemetrexed Disodium | Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC | Active, not recruiting |
| NCT00939770 | Phase Ib/II | Crizotinib | Crizotinib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma | Completed |
| NCT02657434 | Phase III | Cisplatin + Pemetrexed Disodium Carboplatin + Pemetrexed Disodium Atezolizumab + Carboplatin + Pemetrexed Disodium Atezolizumab + Cisplatin + Pemetrexed Disodium | A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower 132) | Active, not recruiting |
| NCT03904108 | Phase II | Ramucirumab | Platinum-Based Chemotherapy Plus Ramucirumab in Patients With Advanced NSCLC Who Have Progressed on First Line Anti-PD-1 Immunotherapy | Recruiting |
| NCT04268550 | Phase II | Selpercatinib | Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) | Recruiting |
| NCT02949843 | Phase II | Nivolumab + Pembrolizumab | Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations | Active, not recruiting |
| NCT03906071 | Phase III | Docetaxel MGCD516 + Nivolumab | Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous NSCLC | Recruiting |