SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.

Abstract

TPS8657 Background: Most patients (pts) with advanced non-small cell lung cancer (NSCLC) will receive treatment with immunotherapy and develop tumor resistance. Several trials investigating combination therapy have not shown benefit over chemotherapy. Additional therapeutic options are needed. Complex clinical trials increase barriers to enrollment. Pragmatic trial designs may overcome challenges with accrual and representativeness in the appropriate setting. S1800A was a randomized phase II trial within Lung-MAP that showed a statistically significant improvement in overall survival (OS) with PR versus SOC for pts with advanced NSCLC who had tumor progression on prior chemotherapy and immunotherapy (JCO 2023). As a follow-on, we designed a pragmatic, randomized, registration intent trial to validate OS results and enhance representative accrual reflecting real-world practice. Methods: S2302 is a registration-intent randomized trial for pts who previously received PD-(L)1 inhibitor therapy for at least 84 days and platinum-based therapy, stratified by immediate prior line of therapy including PD-(L)1 inhibition (yes/no) and PS (0/1 v. 2). Pts are randomized to PR or investigator’s choice SOC (recommended to be based on NCCN guidelines). The primary objective is to compare OS between the arms. The only secondary objective is to summarize serious and unexpected high-grade (Grade 3-4) treatment-related adverse events and all Grade 5 adverse events. The accrual goal is 700 pts based on a design with 85% power to detect a hazard ratio of 0.77, using a 1-sided 2.5% level log-rank test. Estimated accrual duration is 24 months. As of January 2024, 286 pts were randomized, and enrollment is ongoing. S2302 Pragmatica-Lung presents a novel and potentially practice-changing paradigm to conduct a study with a combination of FDA approved drugs with well-known safety profiles and limited toxicity overlap. There are no onerous radiology or specimen requirements, and SOC treatment is provided as per FDA-approved package inserts and institutional policies. The goal is to empower practicing clinicians to enroll pts they see every day by reducing the study barriers and burden of clinical trial participation. The resulting pts enrolled will be more representative than other registration-intent trials. This approach allows the trial to reach more patients and holds the potential to better inform the field across a more representative set of pts with broader impact. Clinical trial information: NCT05633602 .