Objectives
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.