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.

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.