Lee, Jung-YunJung-YunLeeTan, DavidDavidTanRay-Coquard, IsabelleIsabelleRay-CoquardLee, Jung BokJung BokLeeKim, Byoung GieByoung GieKimVan Nieuwenhuysen, ElsElsVan NieuwenhuysenRUBY YUN-JU HUANGTse, Ka YuKa YuTseGonzález-Martin, AntonioAntonioGonzález-MartinScott, ClareClareScottHasegawa, KoseiKoseiHasegawaWilkinson, KatieKatieWilkinsonYang, Eun YeongEun YeongYangLheureux, StephanieStephanieLheureuxKristeleit, RebeccaRebeccaKristeleit2025-05-192025-05-192025-01https://scholars.lib.ntu.edu.tw/handle/123456789/729432Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods: DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinum-based chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent. The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.enCarcinomaGynecologyImmunotherapy[SDGs]SDG3[SDGs]SDG5journal article10.3802/jgo.2025.36.e5139710508