FDA Grants Regular Approval to Dostarlimab-gxly for dMMR Endometrial Cancer

On February 9th, 2023, the U.S. Food and Drug Administration approved dostarlimab-gxly for adult patients with recurrent or advanced endometrial cancer (EC) with mismatch repair deficiency (dMMR) determined by an FDA-approved test, that has progressed or recurred on a platinum-containing regimen and not amenable to curative surgery or radiation.

 

Study ID number: NCT02715284

 

Approval was based on the GARNET trial, a multi-center, single-arm, open-label, phase I study evaluating the anti-programmed death receptor 1 (anti-PD-1) humanized monoclonal antibody dostarlimab (also known as TSR-042) in participants with advanced solid tumors with limited available treatment options. 264 patients with EC were included in the efficacy population, divided into two cohorts, A1 with dMMR/MSI-H disease (108 patients); and A2 with pMMR/MSS disease (156 patients).

 

The first through fourth doses were 500 mg of intravenous infusion of dostarlimab-gxly given over 30 minutes every 3 weeks. After completion of 4 cycles, patients received 1000mg infusion every 6 weeks until disease progression or unacceptable toxicity.

 

Major efficacy outcomes were overall response rate (ORR) and duration of response (DOR).

 

When assessed by blinded independent central review, ORR of 43.5% (95% CI: 34.0%, 53.4%), with 11 complete responses and 36 partial responses was observed after a median follow-up duration of 16.3 months in cohort A1 as compared to ORR of 14.1% (95% CI: 9.1%, 20.6%) with 3 complete responses and 19 partial responses in cohort A2. Median DOR was not reached in either cohort. 85.9% of the patients had DOR of >12 months and 54.7% of the patients had DOR of >24 months.

 

The most common side effects included fatigue, anemia, rash, nausea, vomiting, constipation, and diarrhea. Immune-mediated adverse effects including pneumonitis, colitis, hepatitis, and endocrinopathies among others were also noted infrequently.

 

Thus, dostarlimab demonstrated durable efficacy in both cohorts but predominantly in patients with dMMR disease.

 

References
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer