Safety, Efficacy of Dostarlimab in Patients With Recurrent or Advanced MMR-deficient Endometrial Cancer

In the preliminary data from the trial evaluating dostarlimab, the results demonstrated that the clinical activity in patients with previously treated recurrent or advanced mismatch repair (MMR)-deficient endometrial cancer had an acceptable safety profile.

Dostarlimab is a humanized programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1, and PD-L2. The interim analysis evaluating dostarlimab is meant to assess its safety and efficacy in patients with MMR-deficient endometrial cancer who are also enrolled in the GARNET trial.

For the purposes of the trial, patients were confirmed by immunohistochemistry to have MMR-deficient endometrial cancer before being enrolled. All of these patients had a recurrent or advanced form of the disease and progressed on a platinum doublet regimen. During the trial, the patients received 500 mg Q3W of dostarlimab for the first 4 cycles, then 1000 mg Q6W until the disease progressed or treatment was discontinued.

The primary endpoints of the trial were objective response rate (ORR) and duration of response (DOR), as assessed against Response Evaluation Criteria in Solid Tumors v1.1 by a blinded independent central review.

Seventy

patients with MMR-deficient endometrial cancer treated with dostarlimab were included in this interim analysis. The patients had a median age of 64.5 years, with measurable disease at baseline and ≥6 months of follow-up by the data cutoff point of July 8, 2019. The ORR of the trial was 43%, with 9 (13%) patients confirming complete response and 21 (30%) confirming a partial response.

Of the responders, 77% remained on treatment at the data cutoff point. The Kaplan—Meier estimated likelihood of maintaining response was 96% at 6 months and 77% at 12 months. Furthermore, the disease control rate was 59%, with a median follow-up of 11.2 months at data cutoff; however, median DOR was not reached.

Fifty patients (71%) experienced 1 or more adverse effects (AEs). The most common among these were fatigue, diarrhea, and nausea. Ten (14%) patients had a grade ≥3 AE; among these patients, lipase increased, transaminases increased, and colitis, diarrhea, and anemia (each, 3%) were the most common. Two (3%) patients discontinued treatment due to experiencing these AEs.

Immune-related AEs were reported in 19 (27%) patients, and grade ≥3 immune-related AEs were reported in 7 (10%) patients. For these patients, the most common immune-related AE was diarrhea (6%). There were 4 (6%) deaths due to AEs, none of which were assessed as related to dostarlimab, according to the study.

REFERENCE

Oaknin A, Tinker AV, Gilbert L, et al. Safety and efficacy of the anti—PD-1 monoclonal antibody dostarlimab in patients with recurrent or advanced dMMR endometrial cancer. In: Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer; March 27-March 31, 2020; Toronto, CA. Abstract 9.