FDA Grants Accelerated Approval to Dostarlimab for Advanced dMMR Endometrial Cancer

Officials with the FDA have granted accelerated approval for GlaxoSmithKline’s dostarlimab-gxly (Jemperli; GlaxoSmithKline) for women with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer.

This indication is approved under accelerated approval based on tumor response rate and durability of response.

Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. It is also being investigated as a monotherapy and in combination regimens for women with recurrent or primary advanced endometrial cancer stage 3 or 4 non-mucinous epithelial ovarian cancer for patients with advanced solid tumors or metastatic cancer.

The approval is based on results from the ongoing phase 1 GARNET trial, which includes the largest dataset to date evaluating anti-PD-1 antibody as monotherapy treatment in women with endometrial cancer. Patients in the trial received 500 mg of dostarlimab as an intravenous infusion once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression or unacceptable toxicity.

The primary end points in the trial were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review. According to the results, dostarlimab demonstrated an ORR of 42.3% (95% CI; 30.6-54.6) with a complete response rate of 12.7% and partial response rate of 29.6% among the 71 evaluable patients with dMMR advanced or recurrent endometrial cancer who had progressed on or after treatment with a platinum-containing regimen. Of those that responded, 93.3% demonstrated a DOR of 6 months or more. After a median follow-up of 14.1 months, the median DOR was not reached.

Among the 104 patients evaluable for safety, the most commonly reported adverse effects were fatigue/asthenia, nausea, diarrhea, anemia, and constipation.

“The approval of dostarlimab has the potential to change the way we’ve been treating dMMR advanced or recurrent endometrial cancer after standard platinum-based chemotherapy, especially given the overall response rate and durability of response that we saw in the GARNET trial,” study investigator Jubilee Brown, MD, professor and division director of gynecologic oncology at Levine Cancer Institute, Atrium Health, said in a statement.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Reference

1. FDA grants accelerated approval for GSK’s JEMPERLI (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer. News release. GlaxoSmithKline; April 22, 2021. Accessed April 22, 2021. https://www.gsk.com/en-gb/media/press-releases/fda-grants-accelerated-approval-for-gsk-s-jemperli-dostarlimab-gxly-for-women-with-recurrent-or-advanced-dmmr-endometrial-cancer/