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.
PRIMARY OBJECTIVE: I. To compare overall survival (OS) between participants randomized to docetaxel and ramucirumab with or without cemiplimab (REGN2810) who have acquired resistance to platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To compare investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the arms. II. To compare investigator-assessed response rates (confirmed or unconfirmed, complete response \[CR\] or partial response \[PR\]) per RECIST 1.1 between the arms among participants with measurable disease. III. To compare the investigator-assessed disease control rate (confirmed or unconfirmed, complete response \[CR\], or partial response \[PR\], and stable disease) between the arms. IV. To evaluate the duration of response (DoR) among responders within each arm. V. To evaluate the frequency and severity of toxicities within each arm. VI. To compare investigator-assessed PFS between the arms within the subgroups defined by the stratification factors (histology and performance status) and by PD-L1 subgroups defined as PD-L1 negative (\< 1% tumor proportion score \[TPS\]), intermediate PD-L1 (1-49% TPS), and PD-L1 high (\>= 50% TPS). VII. To compare OS between the arms within the subgroups defined by the stratification factors (histology and performance status) and by PD-L1 subgroups defined as PD-L1 negative (\< 1% TPS), intermediate PD-L1 (1-49% TPS), and PD-L1 high (\>= 50% TPS). TRANSLATIONAL MEDICINE OBJECTIVES: I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at baseline, cycle 3 day 1, and progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA). II. To establish a tissue/blood repository to pursue future studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive dexamethasone orally (PO) twice daily (BID) on days 0-2, ramucirumab intravenously (IV) over 30-60 minutes on day 1 and docetaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. ARM II: Patients receive dexamethasone PO BID on days 0-2, ramucirumab IV over 30-60 minutes on day 1, docetaxel IV over 60 minutes on day 1, and cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, and CT or MRI throughout the study. After completion of study treatment, patients are followed up every 3-6 months for up to 3 years after randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
378
Undergo blood sample collection
Given IV
Undergo CT
Given PO
Given IV
Undergo MRI
Given IV
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne, Alabama, United States
RECRUITINGThomas Hospital
Fairhope, Alabama, United States
RECRUITINGMobile Infirmary Medical Center
Mobile, Alabama, United States
RECRUITINGGulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland, Alabama, United States
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.
Time frame: From date of randomization to date of death due to any cause, assessed up to 3 years
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.
Time frame: From date of randomization to date of first documentation of progression, symptomatic deterioration, or death, whichever comes first, assessed up to 3 years
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.
Time frame: Up to 3 years
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.
Time frame: Up to 3 years
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.
Time frame: From date of first documentation of response by RECIST 1.1 (CR or PR, confirmed or unconfirmed) to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Incidence of adverse events
Adverse events will be assessed and graded using Common Terminology Criteria for Adverse Events version 5.0. Individual toxicities within each treatment arm will be summarized by grade, among those reported as being attributable to treatment (possibly, probably, or definitely attributable to treatment). The frequency and severity for each adverse event term will be summarized for grade 3, 4 and 5 separately, and as worst grade reported overall all reported adverse events.
Time frame: Up to 90 days after last dose of study treatment
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Katmai Oncology Group
Anchorage, Alaska, United States
RECRUITINGBanner University Medical Center - Tucson
Tucson, Arizona, United States
RECRUITINGUniversity of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
RECRUITINGNEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
RECRUITINGKaiser Permanente-Anaheim
Anaheim, California, United States
RECRUITINGKaiser Permanente-Baldwin Park
Baldwin Park, California, United States
RECRUITING...and 376 more locations