Jemperli Plus Chemo Approved for dMMR/MSI-H Advanced or Recurrent Endometrial Cancer

The Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). 

Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody. The approval was based on 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=122), treatment with dostarlimab plus carboplatin-paclitaxel reduced the risk of disease progression by 71% vs placebo plus carboplatin-paclitaxel (hazard ratio [HR], 0.29; 95% CI, 0.17-0.50; P <.0001). The objective response rate (ORR) was 73.8% with dostarlimab (26.2% of patients had complete response and 47.6% had partial response) and 62.2% with placebo (11.1% of patients had complete response and 51.1% had partial response). Median duration of response (DOR) was not reached in the dostarlimab arm; 61.3% of patients had a response lasting greater than 12 months. The DOR was 5.4 months in the placebo arm; 14.3% of patients had a response lasting greater than 12 months. At the time of analysis OS data were immature; the trial continues to assess OS in this subpopulation.

“Today’s expanded approval of Jemperli redefines the treatment landscape for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer,” said Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK. “Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression. In the RUBY trial, Jemperli plus chemotherapy demonstrated a 71% reduction in the risk of disease progression or death vs chemotherapy in this patient population, providing a statistically significant and clinically meaningful benefit. These results and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Jemperli is also indicated 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.