Blossom Mak

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

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. 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. 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. 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. 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. The primary endpoint is the number of participants achieving investigator-assessed pathological complete response within 6 months of treatment. Ten (10) women ≥18 years of age will be enrolled. Accruals are expected to be completed by 2027, with the presentation of results by 2029. NCT06278857.

SATELLITE Study (feaSibility sAfeTy Efficacy dostarLimab earLy-stage defIcient endomeTrial cancEr)

The main goal of this clinical trial is to evaluate dostarlimab, an immunotherapy drug, as a potential alternative to surgery for early-stage endometrial cancer with Mismatch Repair deficiency, a genetic cause for 20-30% of cases. The study aims to establish dostarlimab's efficacy and safety in early-stage endometrial cancer, exploring its potential as a non surgical option for those unsuitable or unwilling to undergo major surgery, allowing for fertility preservation or addressing specific health conditions. Participants will have seven dostarlimab sessions over 12 months. The treatment plan involves four cycles every three weeks, followed by a three-week break, and then three cycles every six weeks. This research is a promising step toward a new, less invasive treatment choice for patients with specific genetic traits. It expands the range of care options for endometrial cancer.