Phase 2b, open-label, single-arm, multicenter pilot study of the efficacy, safety, and tolerability of dostarlimab in women with early-stage mismatch repair-deficient endometrioid endometrial adenocarcinoma

Obermair, A; Gebski, V; Goh, J; Kuchel, A; Brand, A; Mak, B; McNally, O; Baxter, E; Jobling, T; Mileshkin, L

Author(s): Obermair, A; Gebski, V; Goh, J; Kuchel, A; Brand, A; Mak, B; McNally, O; Baxter, E; Jobling, T; Mileshkin, L;
Details: Publication Year 2025-04,Volume 35,Issue #4,Page 101644
Journal Title: International Journal of Gynecological Cancer
Publication Type: Research article
Abstract: BACKGROUND: The standard treatment for endometrial cancer is hysterectomy with or without bilateral salpingo-oophorectomy; however, this may not be an optimal choice for women who have not completed childbearing or who are at a high risk of surgical complications. Conservative treatment with levonorgestrel intrauterine devices appear to be effective in patients with early-stage endometrial cancer; however, patients with mismatch repair-deficient (dMMR) tumors have a low likelihood of responding to levonorgestrel intrauterine devices. PRIMARY OBJECTIVE: To assess the efficacy of dostarlimab, an active immune checkpoint inhibitor that targets the programmed cell death protein-1 receptor, in patients with early-stage dMMR endometrioid endometrial adenocarcinoma. STUDY HYPOTHESIS: Administration of 4 3-weekly cycles of 500 mg dostarlimab followed by a 3-week rest period and 3 6-weekly cycles of 1000 mg dostarlimab will be safe and efficacious in early-stage dMMR endometrial cancer patients. TRIAL DESIGN: Non-randomized, open-label, pilot, multicenter phase2b study designed to evaluate the efficacy and safety of dostarlimab in 10 women aged ≥18 years with a clinically confirmed diagnosis of early-stage and dMMR endometrioid endometrial adenocarcinoma. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically proven stage I, International Federation of Gynecology and Obstetrics grade 1 or 2 dMMR endometrioid endometrial adenocarcinoma and desire for fertility preservation. Exclusions include, but are not limited to, patients with other high-risk endometrial cancer cell types, a poor medical risk due to uncontrolled medical conditions, or those who experienced grade 3 or higher immune-related adverse events from prior immunotherapy. PRIMARY ENDPOINT(S): The primary endpoint is the number of participants achieving investigator-assessed pathological complete response within 6 months of treatment. SAMPLE SIZE: Ten (10) women ≥18 years of age will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accruals are expected to be completed by 2027, with the presentation of results by 2029. TRIAL REGISTRATION: NCT06278857.
Publisher: Elsevier
Keywords: Adult; Aged; Female; Humans; Middle Aged; *Boron Compounds/therapeutic use/adverse effects/administration & dosage; *Carcinoma, Endometrioid/drug therapy/pathology/genetics; Clinical Trials, Phase II as Topic; DNA Mismatch Repair; *Endometrial Neoplasms/drug therapy/pathology/genetics; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use/administration &; dosage; Multicenter Studies as Topic; Neoplasm Staging; Pilot Projects; Antibodies, Monoclonal, Humanized/therapeutic use; Dostarlimab; Endometrial cancer; Fertility-sparing treatment; Mismatch repair
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.ijgc.2025.101644
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-15 04:17:35

Last Modified: 2025-05-15 04:17:57