SWOG S2303: Randomized phase II/III trial of 2nd line nivolumab + paclitaxel + ramucirumab versus paclitaxel + ramucirumab in patients with PD-L1 CPS ≥ 1 advanced gastric and esophageal adenocarcinoma (PARAMUNE).

• DOI: 10.1200/jco.2024.42.3_suppl.tps430
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Anwaar Saeed; Sarah Colby; Paul Eliezer Ober...; Dan G. Duda; Rajiv Agarwal; Colmar Figueroa-M...; Riha Vaidya; Joseph M. Unger; Katherine A. Guthrie; Flavio G Rocha; Maheswari Senthil; Rachael A Safyan; Zev A. Wainberg; Syma Iqbal; E. Gabriela Chiorean; Philip A. Philip
• Keywords: Ramucirumab

TPS430 Background: Anti-VEGFR2 antibody (ramucirumab) has efficacy in gastric cancer (GC), both as monotherapy & combination with paclitaxel based on the REGARD RAINBOW trials that led to its FDA approvals 2 nd line setting. Preclinical data demonstrate significant tumor immune microenvironment modulatory effects from antiangiogenic agents, supporting clinical study of dual VEGFR checkpoint blockade. This resulted at least 7 FDA-approved combinations anti-VEGF/VEGFR anti-PD-1/PD-L1 agents lung, renal, endometrial liver cancers. Recent showed encouraging activity ramucirumab plus nivolumab other pembrolizumab and durvalumab GC esophageal adenocarcinoma. Notably, addition was evaluated a multi-center phase I/II trial. Study population consisted 60% (26/43) harboring tumors positive for PD-L1 CPS ≥ 1. Results revealed (ORR 37.2%, 6-month PFS 46.5%) overall population. Median OS were found be numerically higher 1 (6.4 months 13.8 respectively) compared CPS-negative participants (5.1 8.0 months), suggesting predictive impact this treatment Methods: SWOG2303 is national, randomized, open label, II/III trial assess safety + versus adult patients advanced stage MSS/pMMR Patients must have documented MSI status by standard care tissue-based analysis, evaluable disease imaging, Zubrod performance (PS) 0-1. They should also or radiographic progression intolerance frontline systemic therapy PD-1 inhibitor containing fluoropyrimidine chemotherapy regimen. HER2 are excluded well prior immunotherapy related adverse events (iRAEs) prompted permanent discontinuation agent. Planned enrollment 224. Participants will randomized using dynamic balancing algorithm stratification PS (0 vs 1), location (gastric GEJ esophageal) (≥5 <5). Primary endpoints II III. Secondary include response rate, control safety. Baseline pharmacodynamic changes cellular plasma angiogenic, inflammatory, biomarkers explored correlated efficacy. Other health quality life measured Functional Assessment Cancer Therapy-Gastric (FACT-Ga). Enrollment ongoing.