Phase II randomized study of dostarlimab alone or with bevacizumab versus non-platinum chemotherapy in recurrent gynecological clear cell carcinoma (DOVE/APGOT-OV7/ENGOT-ov80)
- Author(s)
- Lee, JY; Tan, D; Ray-Coquard, I; Lee, JB; Kim, BG; Van Nieuwenhuysen, E; Huang, RY; Tse, KY; González-Martin, A; Scott, C; Hasegawa, K; Wilkinson, K; Yang, EY; Lheureux, S; Kristeleit, R;
- Journal Title
- Journal of Gynecologic Oncology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06023862.
- Keywords
- Carcinoma; Gynecology; Immunotherapy
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.3802/jgo.2025.36.e51
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-21 06:44:57
Last Modified: 2025-01-21 06:46:48