PRIMARY OBJECTIVE:~I. To compare investigator-assessed progression-free survival (IA-PFS) between participants with EGFR mutated, MET amplified non-small cell lung cancer (NSCLC) randomized to INC280 (capmatinib) and osimertinib with or without ramucirumab.~SECONDARY OBJECTIVES:~I. To evaluate if the combination of INC280 (capmatinib), osimertinib and ramucirumab or INC280 (capmatinib) and osimertinib during the first cycle of treatment has an acceptable toxicity rate.~II. To evaluate the frequency and severity of toxicities within the arms. III. To compare IA-PFS between the arms, in the subset of participants with centrally-confirmed MET amplification in tissue.~IV. To compare IA-PFS between the arms, in the subset of participants with centrally-confirmed MET amplification based on circulating tumor deoxyribonucleic acid (ctDNA).~V. To compare IA-PFS between the randomized arms in the subsets of participants with and without history of brain metastases.~VI. To compare the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) between the arms among participants with measurable disease at baseline.~VII. To compare overall survival between the arms. VIII. To compare IA-PFS between the randomized arms in the subsets of patients who have received only 1 prior line of therapy and those who have received 2 or more prior lines of therapy.~IX. To evaluate duration of response among responders within each arm.~TRANSLATIONAL MEDICINE OBJECTIVES:~I. To collect, process, and bank cell-free deoxyribonucleic acid (ctDNA) prior to treatment (Cycle 1 Day 1), Cycle 1 Day 15, Cycle 3 Day 1, and first progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA).~II. To establish a tissue/blood repository from participants with refractory non-small cell lung cancer (NSCLC).~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM A: Patients receive capmatinib orally (PO), osimertinib PO, and ramucirumab intravenously (IV) on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.~ARM B: Patients receive capmatinib PO and osimertinib PO on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.
This phase II Lung-MAP treatment trial test the combination of targeted drugs (capmatinib, osimertinib, and/or ramucirumab) in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has EGFR and MET gene changes. Capmatinib and osimertinib are in a class of medications called kinase inhibitors. They work by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells and may help shrink tumors. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving capmatinib, osimertinib, and/or ramucirumab and targeting abnormal gene changes in tumor cells may be effective in shrinking or stabilizing advanced non-small cell lung cancer.