RAINFOL-03 (ENGOT-EN-31/GOG-3128): A global, phase 3, open-label, randomized study of rinatabart sesutecan (Rina-S) vs investigator’s choice of chemotherapy in patients with endometrial cancer after platinum-based chemotherapy and programmed death-ligand 1 inhibition.

Abstract

TPS5646 Background: Patients with recurrent endometrial cancer (EC) whose disease progresses after platinum-based chemotherapy (PBC) and programmed death (ligand) 1 [PD-(L)1] inhibition have a poor prognosis and limited, ineffective treatment options. Single-agent chemotherapy in this setting has been associated with low objective response rates (ORRs; ~15%) and median progression-free survival (PFS) of ~3-4 months. Rina-S is an investigational antibody-drug conjugate targeting folate receptor alpha (FRα) with a novel hydrophilic protease-cleavable linker and topoisomerase I inhibitor, exatecan, payload. In the phase 1/2 RAINFOL-01 trial (NCT05579366), Rina-S 100 mg/m 2 showed encouraging antitumor activity, with a 50% confirmed ORR, including 2 complete responses, and a manageable safety profile in patients with heavily pretreated EC after progression on PBC and a PD-(L)1 inhibitor (Winer IS, et al. J Clin Oncol . 2025:43[16 suppl]:3039). We report the design of RAINFOL-03, a global, open-label, randomized phase 3 study of Rina-S vs investigator’s choice (IC) therapy in patients with EC who have progressed on PBC and a PD(L)-1 inhibitor (NCT07166094). Methods: This phase 3 open-label study will enroll ~544 patients with recurrent or progressive EC (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma), measurable per RECIST v1.1, who have received 1-3 prior lines of therapy, including PBC and a PD(L)-1 inhibitor. Patients will be randomized 1:1 to receive Rina-S 100 mg/m 2 intravenously every 3 weeks or IC therapy (paclitaxel or doxorubicin) until disease progression or unacceptable toxicity. Patients will be enrolled regardless of FRα expression level; however, FRα expression levels will be required for stratification at randomization. Dual primary endpoints are PFS per RECIST v1.1 by investigator assessment and overall survival. The key secondary endpoint is ORR per RECIST v1.1 by investigator assessment. Additional secondary endpoints include PFS and ORR per RECIST v1.1 by blinded independent central review (BICR), duration of objective response per RECIST v1.1 by investigator assessment and BICR, safety, and quality of life outcomes. The trial is currently recruiting. Clinical trial information: NCT07166094 .