Dostarlimab Under Review for Primary Advanced or Recurrent Endometrial Cancer

The Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application for dostarlimab in combination with chemotherapy for the treatment of adults with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer.

Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody. The sBLA was supported by data from Part 1 of the phase 3 RUBY trial (ClinicalTrials.gov Identifier: NCT03981796), which included women with recurrent or primary advanced (stage III or IV) endometrial cancer. Study participants were randomly assigned to receive dostarlimab plus carboplatin-paclitaxel, followed by dostarlimab or carboplatin-paclitaxel plus placebo, followed by placebo. The primary endpoints were progression free survival (PFS) and overall survival (OS).

Results showed that in the dMMR/MSI-H population (n=118), treatment with dostarlimab plus carboplatin-paclitaxel reduced the risk of disease progression by 72% compared with placebo (estimated PFS at 24 months: 61.4% vs 15.7% for placebo; hazard ratio [HR], 0.28; 95% CI, 0.16-0.50; P <.001).  In the overall population (n=494), PFS was 36.1% in dostarlimab arm and 18.1% in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; P <.001). At 24 months, a clinically meaningful OS trend was observed in patients receiving dostarlimab plus chemotherapy followed by dostarlimab.

“We are excited about this initial filing for this potential new indication for dostarlimab in the patient population that demonstrated the strongest treatment effect in the phase 3 RUBY trial,” said Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK. “Long-term outcomes for patients with primary advanced or recurrent endometrial cancer remain poor, and there is an urgent need to evolve the current standard of care, which is platinum-based chemotherapy. We look forward to working with the FDA and other health authorities as they review this application.”

A regulatory decision is expected on September 23, 2023.

Dostarlimab is currently marketed under the brand name Jemperli for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. It is also approved for patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.