REJOICE-Ovarian01: Phase 3 part of a phase 2/3 study evaluating raludotatug deruxtecan (R-DXd) versus treatment of physician’s choice in patients with platinum-resistant ovarian cancer.

Abstract

TPS5637 Background: Platinum-resistant ovarian cancer (PROC) is associated with poor outcomes. Standard-of-care single-agent non-platinum therapies, with or without bevacizumab, have demonstrated only modest activity in PROC, while targeted therapies remain limited to specific biomarker-defined patient populations. Cadherin-6 (CDH6), a mediator of cell–cell adhesion, is aberrantly expressed in up to 94% of epithelial ovarian cancer tumors. R-DXd is an antibody–drug conjugate comprising a humanized CDH6 antibody covalently linked to a topoisomerase I inhibitor payload (DXd) via a tumor-selective cleavable linker. REJOICE-Ovarian01 is a Phase 2/3 study of R-DXd monotherapy in patients with PROC. Among patients who had completed ≥18 weeks of follow-up or discontinued treatment in the Phase 2 dose-optimization part, the objective response rate (ORR) by blinded independent central review (BICR) was 44.4% (16/36) at 4.8 mg/kg, 50.0% (18/36) at 5.6 mg/kg, and 57.1% (20/35) at 6.4 mg/kg, including three complete responses overall. Clinically meaningful tumor responses were observed irrespective of tumor CDH6 expression, and the safety profile of R-DXd was manageable. R-DXd 5.6 mg/kg was identified as the optimal dose for further evaluation in the Phase 3 part of REJOICE-Ovarian01, which is described here. Methods: The Phase 3 part of REJOICE-Ovarian01 (NCT06161025) is a global, randomized, open-label study of R-DXd in patients with platinum-resistant, high-grade serous or high-grade endometroid ovarian, primary peritoneal, or fallopian tube cancer. Patients must have received 1–4 prior lines of therapy (LOT), including bevacizumab (unless ineligible) and mirvetuximab soravtansine for folate receptor α–positive disease (unless not available locally). Patients are not selected based on tumor CDH6 expression. Approximately 600 patients will be randomized 1:1 to receive either R-DXd 5.6 mg/kg intravenously every 3 weeks until disease progression per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), lost to follow-up, death, or other reason per protocol, or treatment of physician’s choice (TPC; weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan) per local guidelines. Randomization will be stratified by number of prior LOT, tumor CDH6 expression, and by TPC. The primary endpoint is progression-free survival (PFS) by BICR per RECIST 1.1. Key secondary endpoints include overall survival (OS) and quality of life. Stratified log-rank tests will be used to compare PFS and OS between treatment groups. Stratified Cox regression models will be fitted to estimate the hazard ratios for PFS and OS. Enrollment in Phase 3 began in December 2025. Clinical trial information: NCT06161025 .