This phase II/III Expanded Lung-MAP treatment trial compares the effect of adding cemiplimab to docetaxel and ramucirumab versus docetaxel and ramucirumab alone in treating patients with non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Cemiplimab is a monoclonal antibody that stimulates the immune system by blocking the PD-1 pathway. Tumors use the PD-1 pathway to escape attacks from the immune system. By blocking the PD-1 pathway, cemiplimab may help the immune system recognize and attack tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Adding cemiplimab to usual treatment, docetaxel and ramucirumab, may kill more tumor cells compared to docetaxel and ramucirumab alone in treating patients with stage IV or recurrent non-small cell lung cancer.
Participants must have been assigned to S1800E by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1800E is determined by the LUNGMAP protocol
Participants must have measurable or non-measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to randomization
If they experienced disease progression within (≤) 365 days from initiation (cycle 1 day 1) or anti-PD-1 or anti-PD-L1 therapy, this counts as the single allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cemiplimab
Biological/VaccineGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Dexamethasone
DrugGiven PO
Docetaxel
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Ramucirumab
Biological/VaccineGiven IV
Overall survival (OS)
OS will be compared between arms and within the subgroups defined by the stratification factors and by PD-L1 subgroups. Distributions of OS will be estimated using the method of Kaplan-Meier. Hazard ratios for comparisons of OS will be estimated using a Cox Proportional Hazards regression model, with baseline hazard stratification using the stratification factors. Testing will be done using a stratified log-rank test. Confidence intervals (CIs) about medians will be estimated using the method of Brookmeyer-Crowley. For point estimates at landmark times, the associated CIs will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.
Progression-free survival (PFS)
PFS will be compared between arms and within the subgroups defined by the stratification factors and by PD-L1 subgroups. PFS between the arms will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Distributions of PFS will be estimated using the method of Kaplan-Meier. Hazard ratios for comparisons of PFS will be estimated using a Cox Proportional Hazards regression model, with baseline hazard stratification using the stratification factors. Testing will be done using a stratified log-rank test. CIs about medians will be estimated using the method of Brookmeyer-Crowley. For point estimates at landmark times, the associated CIs will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.
Response rates
Response rates (complete response \[CR\] or partial response \[PR\]) between the arms will be assessed per RECIST 1.1. Binary proportions along with confidence intervals will be estimated for response. CIs will be estimated using the Wilson Score method with continuity correction.
Disease control rates
Disease control rates (CR or PR and stable disease) between the arms. Binary proportions along with confidence intervals will be estimated for disease control rate. CIs will be estimated using the Wilson Score method with continuity correction.
Duration of response (DOR)
Will be assessed among participants who achieve a response. Distributions of DOR will be estimated using the method of Kaplan-Meier.
Cell-free deoxyribonucleic acid
Tissue/blood repository
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SWOG Cancer Research Network
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
National Cancer Institute (NCI)
Collaborator
