SWOG S2302, PRAGMATICA-LUNG: A pragmatic trial designed to increase participant representation.

Abstract

11016 Background: Effective therapy following frontline immune checkpoint inhibitor (ICI)-based treatment for advanced non-small cell lung cancer (NSCLC) is needed as limited options are available. Lung-MAP S1800A was a Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care (SOC) for patients with NSCLC previously treated with immunotherapy that demonstrated benefit in overall survival (OS) with an improved toxicity profile over SOC. S2302 Pragmatica-Lung trial was pragmatically designed to evaluate the impact on OS while reducing barriers to participation and decreasing clinical trial staff burden. We assessed reduction in barriers to participation and clinical staff burden in S2302 in relationship to S1800A. Methods: S2302 (NCT05633602) is a registration-intent randomized phase III trial for patients with advanced NSCLC 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). The pragmatic design has limited eligibility criteria, which are focused on stage, prior therapy and safety to enroll patients as would occur in real world practice. Laboratory assessment and imaging with RECIST reads are not required due to the OS endpoint. Data collection was developed to minimize the burden with fewer time points for data submitted, number of forms and number of data elements. Concomitant medications are not collected. Given the known safety profile of both study drugs, only related and unexpected grade 3/4 and all grade 5 adverse events are collected. Results: Accrual to S2302 was robust with 838 patients enrolled from March 2023 to December 2024 (21 months), averaging > 50 patients/month in the final 6 months. The trial enrolled 77% White and 13% Black patients. versus 87% and 8%, respectively on S1800A. Over 65% were ≥ 65 years of age. Reduced data collection on S2302 relative to S1800A results in an estimated decrease in the number of forms and data elements submitted within the first year on study by 45% and 66%, respectively. Conclusions: Incorporating pragmatic elements into S2302 resulted in robust accrual, increased participant representativeness and access for patients. The reduced burden on staff due to decreased data forms and elements is substantial. Pragmatic design elements should be considered as we develop trials to generalize to a broad and representative population. Clinical trial information: NCT05633602 .