This phase III trial compares the effect of the combination of ramucirumab and pembrolizumab versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving ramucirumab with pembrolizumab is more effective at treating patients with stage IV or recurrent non-small cell lung cancer than standard chemotherapy.
PRIMARY OBJECTIVE: I. To compare overall survival (OS) in participants previously treated with platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC) randomized to pembrolizumab and ramucirumab versus standard of care. SECONDARY OBJECTIVE: I. To summarize reports of serious and unexpected high-grade (\>= grade 3) treatment-related adverse events determined by the treating physician within each treatment arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive chemotherapy per standard of care on study. ARM B: Patients receive ramucirumab intravenously (IV) and pembrolizumab IV on study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
838
Receive standard of care chemotherapy
Given IV
Given IV
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, United States
Overall survival
Assessed in participants with stage IV or recurrent non-small cell lung cancer with acquired resistance to anti-PD-1 or anti-PD-L1 therapy randomized to ramucirumab and pembrolizumab or standard of care chemotherapy. Will use an intention-to-treat analysis and the comparison will be done using a stratified log-rank test. The distribution of overall survival will be estimated using the method of Kaplan-Meier and a Cox proportional hazards model will be used to estimate hazard ratios and associated 95% confidence intervals to estimate treatment effects.
Time frame: From date of randomization to date of death due to any cause, assessed up to 3 years
Incidence of high-grade (>= grade 3) adverse events
Unexpected treatment-related adverse events determined by the treating physician.
Time frame: Up to 3 years
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Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
John L McClellan Memorial Veterans Hospital
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Highlands Oncology Group - Rogers
Rogers, Arkansas, United States
Highlands Oncology Group
Springdale, Arkansas, United States
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