RAINFOL-04 (ENGOT-OV96/GOG-3134): A phase 3, open-label, randomized study of rinatabart sesutecan (Rina-S) plus standard of care (SOC) vs SOC as maintenance treatment after second-line platinum-based chemotherapy in patients with recurrent platinum-sensitive ovarian cancer.

Abstract

TPS5641 Background: Ovarian cancer (OC) is the eighth leading cause of cancer-related death in women globally. In patients with advanced OC, 70%-80% develop recurrent platinum-sensitive OC (PSOC) within 3 years after initial therapy. Standard treatment for recurrent PSOC includes platinum-based chemotherapy ± bevacizumab (BEV), but in most patients, disease progression occurs within a year. Rina-S is an antibody-drug conjugate targeting folate receptor alpha (FRα) with a novel hydrophilic protease-cleavable linker and a topoisomerase I inhibitor, exatecan, payload. In cohort B1 of the phase 1/2 RAINFOL-01 study (NCT05579366), Rina-S showed encouraging antitumor activity and was tolerated in patients with heavily pretreated advanced OC. We report the design of ENGOT-OV96/GOG-3134 (RAINFOL-04), a phase 3, randomized study of Rina-S + standard of care (SOC) vs SOC as maintenance treatment for patients with recurrent PSOC (NCT07225270). Methods: This phase 3 open-label study will enroll ~528 patients with platinum-sensitive high-grade serous or endometrioid epithelial OC, primary peritoneal cancer, or fallopian tube cancer regardless of their FRα expression. Patients must have disease progression >6 months after the last dose of first-line platinum chemotherapy and have achieved at least stable disease following completion of second-line platinum-based chemotherapy ± BEV. Patients will be randomized 1:1 to receive Rina-S 120 mg/m 2 intravenously every 3 weeks plus SOC or SOC (BEV or observation) until disease progression, unacceptable toxicity, or discontinuation. The primary endpoint is progression-free survival (PFS) per RECIST v1.1 by investigator assessment. The key secondary endpoint is overall survival. Additional secondary endpoints include PFS per RECIST v1.1 by blinded independent central review, PFS2 (time from randomization to the second progression or death), safety, and patient-reported outcomes. The trial is currently recruiting. Clinical trial information: NCT07225270 .