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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Undergo collection of blood samples
Given PO
Undergo CT scan
Undergo MRI
Given PO
Given IV
Katmai Oncology Group
Anchorage, Alaska, United States
RECRUITINGKingman Regional Medical Center
Kingman, Arizona, United States
RECRUITINGCancer Center at Saint Joseph's
Phoenix, Arizona, United States
SUSPENDEDNEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
Investigator-assessed progression-free survival
Will be estimated using the method of Kaplan-Meier. Medians and their associated 95% confidence intervals will be estimated using the Brookmeyer-Crowley method. Binary proportions and the associated confidence interval will be estimated.
Time frame: From date of sub-study randomization to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Duration of response
Will be estimated using the method of Kaplan-Meier. Medians and their associated 95% confidence intervals will be estimated using the Brookmeyer-Crowley method. Binary proportions and the associated confidence interval will be estimated.
Time frame: From date of first documentation of response to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a response, assessed up to 3 years
Dose limiting toxicity (DLT)
Treatment-related Grade 3 or higher non hematologic toxicity, treatment-related Grade 4 or higher hematologic toxicity, or any grade of treatment-related toxicity that leads to drug discontinuation. The DLT assessment period is the first cycle of treatment. Treatment related is defined as an attribution of possible, probably, or likely related to treatment. Toxicities to be graded based on Common Terminology Criteria for Adverse Events.
Time frame: Up to 3 years
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University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
RECRUITINGKaiser Permanente-Anaheim
Anaheim, California, United States
ACTIVE_NOT_RECRUITINGMission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California, United States
SUSPENDEDPCR Oncology
Arroyo Grande, California, United States
RECRUITINGSutter Auburn Faith Hospital
Auburn, California, United States
RECRUITINGKaiser Permanente-Baldwin Park
Baldwin Park, California, United States
ACTIVE_NOT_RECRUITING...and 438 more locations