| Profile Name | ALK rearrange |
| 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 rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Alectinib | Clinical Study | Actionable | In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117). | 26438117 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Alectinib | FDA approved | Actionable | In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). | 28586279 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Alectinib | Phase II | Actionable | In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). | 26598747 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Alectinib | Guideline | Actionable | Alecensa (alectinib) is included in guidelines as the preferred first-line therapy for patients with ALK-rearranged, metastatic non-small cell lung cancer, and as the subsequent therapy for patients who have progressed after Xalkori (crizotinib) (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | no benefit | Afatinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib | Guideline | Actionable | Zykadia (ceritinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer patients, and as subsequent therapy in patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib | FDA approved | Actionable | In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). | 25754348 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib | Phase III | Actionable | In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099). | 28126333 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib | Clinical Study | Actionable | In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117). | 26438117 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib | Phase II | Actionable | In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060). | 27432917 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ceritinib + Crizotinib | Clinical Study | Actionable | In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). | 25724526 | ALK rearrange | non-small cell lung carcinoma | no benefit | Pembrolizumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | no benefit | Pembrolizumab | Clinical Study | Actionable | In a retrospective study, 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 | Advanced Solid Tumor | sensitive | ALK Inhibitor | ASP3026 | Phase I | Actionable | In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). | 26966027 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Crizotinib | Phase III | Actionable | In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). | 27022118 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Crizotinib | Phase III | Actionable | In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Crizotinib | FDA approved | Actionable | In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). | 25470694 | ALK rearrange | Advanced Solid Tumor | sensitive | ALK Inhibitor | Entrectinib | Phase I | Actionable | In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). | detail... | ALK rearrange | Advanced Solid Tumor | sensitive | ALK Inhibitor | Entrectinib | Phase I | Actionable | In a clinical study analyzing combined results of 2 Phase I trials, Entrectinib (RXDX-101) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients received prior Alk inhibitor treatments (PMID: 28183697). | 28183697 | ALK rearrange | non-small cell lung carcinoma | no benefit | Atezolizumab | Clinical Study | Actionable | In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 | ALK rearrange | non-small cell lung carcinoma | no benefit | Atezolizumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | no benefit | Durvalumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | no benefit | Durvalumab | Clinical Study | Actionable | In a retrospective study, 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 | non-small cell lung carcinoma | no benefit | Gefitinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | no benefit | Nivolumab | Clinical Study | Actionable | In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 | ALK rearrange | non-small cell lung carcinoma | no benefit | Nivolumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | 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 crizotinib-treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716). | 27836716 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Brigatinib | Clinical Study | Actionable | In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulted in objective response in 17% (3/18) and stable disease in 50% (9/18) of patients with alectinib-refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). | 29935304 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines as subsequent therapy for ALK rearranged non-small cell lung cancer patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Brigatinib | Clinical Study | Actionable | In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). | 26438117 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Brigatinib | FDA approved | Actionable | In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). | 28475456 | ALK rearrange | non-small cell lung carcinoma | no benefit | Osimertinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Lorlatinib | FDA approved | Actionable | In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (103/215, 4% complete response, 44% partial response) in ALK-rearranged non-small cell lung carcinoma patients that had received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865). | detail... | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). | 29074098 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Lorlatinib | Phase II | Actionable | IIn a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 90% (27/30; 1 complete response (CR) and 26 partial responses (PR)) and an intracranial response rate of 66.7% (2/3) in treatment-naive non-small cell lung cancer (NSCLC) patients harboring an ALK rearrangement, and an OR rate of 47% (93/198; 4 CR, 89 PR) and an objective intracranial response rate of 63% (51/81) in ALK-rearranged NCSLC patients that had received prior therapy (PMID: 30413378; NCT01970865). | 30413378 | ALK rearrange | non-small cell lung carcinoma | 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 | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ensartinib | Phase Ib/II | Actionable | In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months (PMID: 29563138; NCT01625234). | 29563138 | ALK rearrange | non-small cell lung carcinoma | sensitive | ALK Inhibitor | Ensartinib | Clinical Study | Actionable | In a retrospective study, 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 |
|---|
| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT01772004 | Phase I | Avelumab | Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor) | Active, not recruiting |
| NCT03421353 | Phase Ib/II | AZD9150 + Cisplatin + Durvalumab + Gemcitabine AZD9150 + Carboplatin + Durvalumab + Gemcitabine AZD9150 + Cisplatin + Durvalumab + Fluorouracil AZD9150 + Durvalumab AZD9150 + Carboplatin + Durvalumab + Nab-paclitaxel | AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer | Recruiting |
| NCT02750215 | Phase II | Capmatinib | A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor | Recruiting |
| NCT01744652 | Phase I | Crizotinib + Dasatinib | Dasatinib and Crizotinib in Advanced Cancer | Active, not recruiting |
| NCT03417037 | Phase III | BMS-986205 + Nivolumab | An Immuno-Therapy Study of Experimental Medication BMS-986205 Given With Nivolumab With or Without Chemotherapy Compared to Chemotherapy in Participants With Previously Untreated Stage IV or Recurrent Non-Small Cell Lung Cancer | Withdrawn |
| NCT01579994 | Phase I | Ganetespib + Crizotinib | Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers | Active, not recruiting |
| NCT02393625 | Phase I | Ceritinib + Nivolumab | Study of Safety and Efficacy of Ceritinib in Combination With Nivolumab in Patients With ALK-positive Non-small Cell Lung Cancer | Recruiting |
| NCT03647488 | Phase II | INC280 + PDR001 Docetaxel | Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer | Recruiting |
| NCT02314364 | Phase II | A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC | Recruiting | |
| NCT02264990 | Phase III | Pemetrexed Carboplatin Paclitaxel Veliparib Cisplatin | Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer Who Are Current or Former Smokers | Active, not recruiting |
| NCT02864992 | Phase II | Tepotinib | Tepotinib Phase II Study in Lung Adenocarcinoma Harbouring MET Exon 14 (METex14) Skipping Alterations | Recruiting |
| NCT03275597 | Phase I | Durvalumab + Tremelimumab | Phase Ib Study of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Non-small Lung Cancer (NSCLC) With Dual Immune Checkpoint Inhibition | Recruiting |
| NCT03179436 | Phase I | MK-1308 + Pembrolizumab | Safety, Pharmacokinetics (PK), and Efficacy of MK-1308 in Combination With Pembrolizumab in Advanced Solid Tumors (MK-1308-001) | Recruiting |
| NCT02422589 | Phase I | Warfarin Midazolam Ceritinib | A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors | Completed |
| NCT02352948 | Phase III | Durvalumab Erlotinib + Gemcitabine + Vinorelbine Durvalumab + Tremelimumab Tremelimumab | A Global Study to Assess the Effects of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer | Active, not recruiting |
| NCT02091141 | Phase II | Erlotinib Alectinib Vemurafenib + Cobimetinib Pertuzumab + Trastuzumab Vismodegib Atezolizumab | My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors | Recruiting |
| NCT02495636 | Phase II | Atezolizumab + DEC-205-NY-ESO-1 fusion protein vaccine | Phase 2 Study of MPDL3280A Combined With CDX-1401 in NY-ESO 1 (+) IIIB, IV or Recurrent Non-Small Cell Lung Cancer | Withdrawn |
| NCT03516981 | Phase II | MK-4280 + Pembrolizumab Lenvatinib + Pembrolizumab | A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495) | Recruiting |
| NCT03308942 | Phase II | Niraparib | Phase 2, Multi-Arm Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer | Recruiting |
| NCT01798485 | Phase III | Ganetespib Docetaxel | A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC | Terminated |
| NCT03003962 | Phase III | Durvalumab Gemcitabine + Cisplatin Carboplatin + Gemcitabine Carboplatin + Pemetrexed Cisplatin + Pemetrexed Paclitaxel + Carboplatin | Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer | Active, not 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 |
| NCT02292550 | Phase Ib/II | Ceritinib + LEE011 | Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer. | Completed |
| NCT02544633 | Phase II | Glesatinib | Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET | Completed |
| NCT03256136 | Phase II | Carboplatin + Nivolumab + Pemetrexed Nivolumab + Ipilimumab | A Phase II Study of Nivolumab in Combination With Carboplatin and Pemetrexed, or Nivolumab in Combination With Ipilimumab, in Patients With Advanced, EGFR-mutant or ALK-rearranged, Non-Small Cell Lung Cancer | Recruiting |
| NCT02094573 | Phase II | Brigatinib | A Phase 2, Multicenter, Randomized Study of AP26113 | Active, not recruiting |
| NCT03302234 | Phase III | Pembrolizumab Ipilimumab + Pembrolizumab | Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-small Cell Lung Cancer (MK-3475-598/KEYNOTE-598) | Recruiting |
| NCT01948141 | Phase II | Nintedanib | Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens | Completed |
| NCT02041533 | Phase III | Nivolumab Paclitaxel Cisplatin Pemetrexed Carboplatin Gemcitabine | An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026) | Active, not recruiting |
| NCT01712217 | Phase Ib/II | Crizotinib AT13387 | A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib | Completed |
| NCT03611738 | Phase I | Ceritinib + Docetaxel | Ceritinib Plus Docetaxel in ALK-Negative, EGFR WT Advanced NSCLC | Recruiting |
| NCT02382406 | Phase Ib/II | Pembrolizumab Carboplatin + nab-paclitaxel | Carboplatin/Nab-Paclitaxel and MK-3475 in NSCLC | Recruiting |
| NCT03131206 | Phase Ib/II | Alectinib | A Study of Alectinib in RET-rearranged Non-small Cell Lung Cancer or RET-mutated Thyroid Cancer | Active, not recruiting |
| NCT03023904 | Phase II | Nivolumab | Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads | Withdrawn |
| NCT02521051 | Phase Ib/II | Bevacizumab Alectinib | Phase I/II Trial of Alectinib and Bevacizumab in Patients With Advanced, Anaplastic Lymphoma Kinase (ALK)-Positive, Non-Small Cell Lung Cancer | Recruiting |
| NCT01803282 | Phase I | GS-5745 Fluorouracil + Leucovorin + Oxaliplatin + Pembrolizumab Carboplatin + Pemetrexed FOLFIRI Nab-paclitaxel + Gemcitabine Paclitaxel + Carboplatin Paclitaxel Bevacizumab | Safety and Tolerability Study in Solid Tumors | Active, not recruiting |
| NCT03233724 | Phase Ib/II | Pembrolizumab | The Immune Checkpoint Inhibitor Pembrolizumab in Combination With Oral Decitabine and Tetrahydrouridine as First-Line Therapy for Inoperable, Locally Advanced or Metastatic Non-small Cell Lung Cancer | Recruiting |
| NCT02568267 | Phase II | Entrectinib | Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK1/2/3, ROS1, or ALK Gene Rearrangements (STARTRK-2) | Recruiting |
| NCT02400814 | Phase I | Atezolizumab | MPDL3280A and Stereotactic Ablative Radiotherapy in Patients With Non-small Cell Lung Cancer | Recruiting |
| NCT03665129 | Phase I | Durvalumab + IPH5401 | IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors | Recruiting |
| NCT03093116 | Phase Ib/II | Ropotrectinib | A Study of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements | Recruiting |
| NCT03456076 | Phase III | Carboplatin + Cisplatin + Gemcitabine + Pemetrexed + Vinorelbine Alectinib | A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Participants With ALK Positive Non-Small Cell Lung Cancer | Recruiting |
| NCT03157128 | Phase I | LOXO-292 | Phase 1 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET-Fusion Lung Cancer and Medullary Thyroid Cancer | Recruiting |
| NCT03130764 | Phase II | Durvalumab + Tremelimumab | Durvalumab and Tremelimumab for Adjuvant Therapy of Resected NSCLC | Withdrawn |
| NCT03322566 | Phase III | Epacadostat + Pembrolizumab Paclitaxel + Carboplatin Cisplatin + Pemetrexed Carboplatin + Pemetrexed | Pembrolizumab Plus Epacadostat Alone or With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer | Active, not recruiting |
| NCT03158883 | Phase I | Avelumab | Avelumab and Stereotactic Ablative Radiotherapy in Non-responding and Progressing NSCLC Patients | Recruiting |
| NCT02650401 | Phase I | Entrectinib | Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors | Recruiting |
| NCT02706626 | Phase II | Brigatinib | Trial of Brigatinib After Treatment With Second-Generation ALK Inhibitors | Recruiting |
| NCT02259114 | Phase I | Birabresib | A Phase IB Trial With OTX015, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Patients With Selected Advanced Solid Tumors | Completed |
| NCT03268057 | Phase Ib/II | Avelumab + VX15/2503 | VX15/2503 in Combination With Avelumab in Advanced Non-small Cell Lung Cancer | Recruiting |
| NCT03178071 | Expanded access | Lorlatinib | Expanded Access For Lorlatinib For Patients With Non Small Cell Lung Cancer Harboring Specific Molecular Alterations | No longer available |
| NCT03425331 | Phase II | Nivolumab + Ipilimumab | Biomarkers of Response to Ipilimumab and Nivolumab in First-line NSCLC | Recruiting |
| NCT01970865 | Phase Ib/II | Lorlatinib Crizotinib | A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations | Active, not recruiting |
| NCT02231164 | Phase III | Docetaxel Nintedanib | LUME-Columbus: Nintedanib Plus Docetaxel in Advanced Non-small Cell Lung Cancer With Translational Research | Terminated |
| NCT03559049 | Phase Ib/II | Carboplatin + Pembrolizumab + Pemetrexed + Rucaparib | Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer | Recruiting |
| NCT02504489 | Phase III | Docetaxel Docetaxel + Plinabulin | Plinabulin (P) + Docetaxel (D) vs D as 2nd-Line Chemo in Patients With Advanced NSCLC With at Least 1 Large Lung Lesion | Recruiting |
| NCT03202940 | Phase Ib/II | Alectinib + Cobimetinib | A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC | Recruiting |
| NCT02898116 | Phase Ib/II | MEDI4736 + X-396 Ensartinib | A Study of ALK Inhibitor, Ensartinib, and Anti-PD-L1, Durvalumab, in Subjects With ALK-rearranged Non-small Cell Lung Cancer | Completed |
| NCT03064854 | Phase I | Carboplatin + Paclitaxel + PDR001 Cisplatin + Pemetrexed + PDR001 Cisplatin + Gemcitabine + PDR001 Pemetrexed + PDR001 + Cisplatin + Carboplatin | PDR001 in Combination With Platinum-doublet Chemotherapy in PD-L1 Unselected, Metastatic NSCLC Patients (ElevatION:NSCLC-101 Trial) | Recruiting |
| NCT03215706 | Phase III | Carboplatin + Cisplatin + Paclitaxel + Pemetrexed Nivolumab + Ipilimumab | A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy by Itself as the First Treatment Given for Stage IV Non-Small Cell Lung Cancer (NSCLC) (CheckMate 9LA) | Recruiting |
| NCT03322540 | Phase III | Pembrolizumab Epacadostat + Pembrolizumab | Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer | Active, not recruiting |
| NCT02185690 | Phase I | MEK162 + Carboplatin + Pemetrexed | A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung | Recruiting |
| NCT02513667 | Phase II | Ceritinib | Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma | Recruiting |
| NCT02733250 | Phase Ib/II | nab-paclitaxel + Pembrolizumab | Pembrolizumab With Nab-Paclitaxel in Non-Small Cell Lung Cancer (URCOH-PMS-001) | Active, not recruiting |
| NCT03535740 | Phase II | Brigatinib | A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib | Recruiting |
| NCT02277457 | Phase I | Crizotinib Erlotinib | Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations | Withdrawn |
| NCT01871805 | Phase Ib/II | Alectinib | A Study of CH5424802/RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer | Completed |
| NCT03664024 | Phase II | Pemetrexed + Pembrolizumab Carboplatin + Pembrolizumab + Pemetrexed Cisplatin + Pembrolizumab + Pemetrexed | Biomarkers of Response to Pembrolizumab Combined With Chemotherapy in Non-Small Cell Lung Cancer (KEYNOTE-782, MK-3475-782) (KEYNOTE-782) | Recruiting |
| NCT03472560 | Phase II | Avelumab + Axitinib | A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF) | Recruiting |
| NCT01784640 | Phase I | Luminespib + Pemetrexed | Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non-Small Cell Lung Cancer | Active, not recruiting |
| NCT03707938 | Phase I | Brigatinib | Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer | Recruiting |
| NCT03631706 | Phase II | M7824 Pembrolizumab | M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC) | Recruiting |
| NCT03270176 | Phase I | AT-406 + Avelumab | A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy | Recruiting |
| NCT02879617 | Phase II | Durvalumab | A Clinical Trial of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer Patients | Recruiting |
| NCT02823990 | Phase II | MVA-MUC1-IL2 vaccine + Nivolumab | TG4010 and Nivolumab in Patients With Lung Cancer | Active, not recruiting |
| NCT03048136 | Phase III | Nivolumab + Ipilimumab | A Safety Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Non-small Cell Lung Cancer (CheckMate 955) | Withdrawn |
| NCT03313778 | Phase I | mRNA-4157 + Pembrolizumab mRNA-4157 | Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors (KEYNOTE-603) | Recruiting |
| NCT02289144 | Phase II | Ceritinib | Ceritinib (LDK378) in Mutation and Oncogene Directed Therapy in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer | Recruiting |
| NCT02414139 | Phase II | Capmatinib | Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With Advanced Non-small Cell Lung Cancer Who Have Received One or Two Prior Lines of Therapy | Recruiting |
| NCT03468985 | Phase II | Cabozantinib + Nivolumab Cabozantinib + Ipilimumab + Nivolumab Nivolumab | Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer | Suspended |
| NCT02336451 | Phase II | Ceritinib | A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges | Completed |
| NCT02259582 | Phase II | Carboplatin + Pemetrexed Demcizumab | A Study of Carboplatin, Pemetrexed Plus Placebo vs Carboplatin, Pemetrexed Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With Non-Squamous Non-Small Cell Lung Cancer | Completed |
| NCT01772797 | Phase I | Ceritinib Luminespib | Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer | Completed |
| NCT03696212 | Phase Ib/II | Grapiprant + Pembrolizumab | Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma | Recruiting |
| NCT02654587 | Phase III | OSE 2101 Docetaxel + Pemetrexed | Study of OSE2101 Versus Standard Treatment as 2nd or 3rd Line in HLA-A2 Positive Patients With Advanced NSCLC (ATALANTE 1) | Recruiting |
| NCT01935336 | Phase II | Ponatinib | Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers | Active, not recruiting |
| NCT01449461 | Phase Ib/II | Brigatinib | A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113 | Active, not recruiting |
| NCT03087448 | Phase Ib/II | Ceritinib + Trametinib | Ceritinib + Trametinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC) | Recruiting |
| NCT02453282 | Phase III | Durvalumab Gemcitabine + Cisplatin Paclitaxel + Carboplatin Tremelimumab | Phase III Open Label First Line Therapy Study of MEDI 4736 With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC). | Active, not recruiting |
| NCT03430063 | Phase II | Ipilimumab + REGN2810 Cemiplimab | A Study of REGN2810 and Ipilimumab in Patients With Lung Cancer | Recruiting |
| NCT03220477 | Phase I | Guadecitabine + Mocetinostat + Pembrolizumab | Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer. | Recruiting |
| NCT03164772 | Phase Ib/II | BI 1361849 + Durvalumab + Tremelimumab | Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With NSCLC | Recruiting |
| NCT02465060 | Phase II | Dabrafenib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Binimetinib Adavosertib Osimertinib Trastuzumab Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib trastuzumab emtansine Larotrectinib Pertuzumab Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting |
| NCT02578680 | Phase III | Carboplatin Pembrolizumab Pemetrexed Cisplatin | Study of Platinum+Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Non-squamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189) | Active, not recruiting |
| NCT02271139 | Phase III | Alectinib | Expanded Access Study of Alectinib for Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Crizotinib | No longer available |
| NCT03317496 | Phase II | Avelumab + Cisplatin + Gemcitabine Avelumab + Carboplatin + Pemetrexed | Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies | Recruiting |
| NCT03156114 | Phase I | BI 754091 BI 754111 | This Study Tests the New Medicine BI 754111 Alone or in Combination With Another New Substance BI 754091 in Patients With Advanced Cancer. The Study Tests Different Doses to Find the Best Dose for Continuous Treatment. | Recruiting |
| NCT03194893 | Phase III | Crizotinib Alectinib | A Roll Over Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer | Recruiting |
| NCT02451865 | Phase I | Binimetinib + Docetaxel | Binimetinib With Docetaxel in Treating Patients With Previously Treated, Stage IV Non-small Cell Lung Cancer | Withdrawn |
| NCT02473497 | Expanded access | Crizotinib | Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients | Available |
| NCT02848651 | Phase II | Atezolizumab | A Study of Atezolizumab (MPDL3280A) as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC): Clinical Evaluation of Novel Blood-Based Diagnostics [B-F1RST] | Active, not recruiting |
| NCT03138889 | Phase I | NKTR-214 + Pembrolizumab | A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Metastatic Urothelial Bladder Cancer or Metastatic Non-Small Cell Lung Cancer | Recruiting |
| NCT02927340 | Phase II | Lorlatinib | A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions | Recruiting |
| NCT02395172 | Phase III | Avelumab Docetaxel | Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200) | Active, not recruiting |
| NCT03286296 | Phase I | LZM009 | LZM009 to Treat Patients With Advanced Solid Tumors | Recruiting |
| NCT02784158 | Phase I | Brigatinib | An Expanded Access Study of Brigatinib for Patients With ALK-positive Advanced Non-Small Cell Lung Cancer | No longer available |
| NCT03409614 | Phase III | Ipilimumab + REGN2810 Cemiplimab | REGN2810 (Anti-PD-1 Antibody), Ipilimumab (Anti-CTLA-4 Antibody), and Platinum-based Doublet Chemotherapy in Patients With Lung Cancer | Recruiting |
| NCT03088930 | Phase II | Crizotinib | Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer | Recruiting |
| NCT03348904 | Phase III | Carboplatin + Cisplatin + Gemcitabine + Nivolumab + Paclitaxel + Pemetrexed Carboplatin + Cisplatin + Gemcitabine + Paclitaxel + Pemetrexed Carboplatin + Cisplatin + Epacadostat + Gemzar + Nivolumab + Taxol + Pemetrexed | Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer | Terminated |
| NCT03515629 | Phase III | Ipilimumab + REGN2810 Pembrolizumab | REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer | Recruiting |
| NCT03425006 | Phase II | Itacitinib + Pembrolizumab | Pembrolizumab and Itacitinib (INCB039110) for NSCLC | Recruiting |
| NCT02737501 | Phase III | Brigatinib Crizotinib | ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in ALK-positive Advanced Non-Small Cell Lung Cancer Patients | Active, not recruiting |
| NCT02142738 | Phase III | Cisplatin Paclitaxel Carboplatin Gemcitabine Pembrolizumab Pemetrexed | Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024) | Active, not recruiting |
| NCT02576574 | Phase III | Gemcitabine Paclitaxel Cisplatin Avelumab Pemetrexed Carboplatin | Avelumab in First-line Non-Small Cell Lung Cancer (JAVELIN Lung 100) | Active, not recruiting |
| NCT02542293 | Phase III | Gemcitabine + Cisplatin Carboplatin + Gemcitabine Durvalumab + Tremelimumab Paclitaxel + Carboplatin Cisplatin + Pemetrexed Carboplatin + Pemetrexed | Study of 1st Line Therapy Study of MEDI4736 With Tremelimumab Versus SoC in Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE). | Active, not recruiting |
| NCT02350764 | Phase II | Nivolumab | Evaluate the Mediators of Sensitivity and Resistance to Nivolumab in Patients With Advanced NSCLCs | Recruiting |
| NCT03371381 | Phase Ib/II | JNJ-64041757 + Nivolumab Nivolumab | An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung | Terminated |
| NCT02696993 | Phase Ib/II | Nivolumab Ipilimumab | Phase I/II Trial of Nivolumab With Radiation or Nivolumab and Ipilimumab With Radiation for the Treatment of Intracranial Metastases From Non-small Cell Lung Cancer | Recruiting |