FDA Expands Dostarlimab Approval for All Advanced Endometrial Cancers

• The FDA has expanded the approval of dostarlimab-gxly (Jemperli) plus standard-of-care chemotherapy to include all forms of advanced endometrial cancer.
• This includes patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) tumors.
• The approval is supported by data from the RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).

Dostarlimab plus chemotherapy is now approved for all forms of advanced endometrial cancer, including for patients with pMMR/MSS tumors.¹

In July 2023, the FDA approved dostarlimab plus chemotherapy in MRR-deficient (dMMR) and microsatellite instability-high (MSI-H) endometrial cancer.² Findings from the phase 3 RUBY trial support this approval. 

Data from part 1 of the study were presented at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and showed that the median overall survival (OS) was 44.6 months (95% CI, 32.6-not estimated [NE]) and 28.2 months (95% CI, 22.1-35.6) with dostarlimab and placebo/chemotherapy, respectively (HR, 0.69; 95% CI, 0.54-0.89; P = .002) at 51.2% maturity and a median follow-up of 37.2 months.³ These findings crossed the prespecified stopping boundary for OS (P = .01101) and were both statistically significant and clinically relevant. At 2 and 3 years, the OS rates among patients in the dostarlimab arm were 70.1% and 54.9%, respectively. In the placebo arm, these rates were 54.3% and 42.9%, respectively.

In the pMMR/MSS subgroup, the median OS was 34.0 months (95% CI, 28.6-NE) with dostarlimab vs 27.0 months (95% CI, 21.5-35.6) with placebo (HR, 0.79; 95% CI, 0.60-1.04) at a median follow-up of 37.5 months. The OS maturity rate was 54.8%. At 2 and 3years, the OS rates were 66.5% and 48.6% with dostarlimab, respectively, and were 53.2% and 41.9%, respectively, with placebo.

In patients whose tumors dMMR/MSI-H at a median follow-up of 36.6 months, the maturity rate was 39.8% at a median follow-up of 36.6 months. Here, the median OS was NE (95% CI, NE-NE) with dostarlimab vs 31.4 months (95% CI, 20.3-NE) for placebo (HR, 0.32; 95% CI, 0.17-0.63), The 2- and 3-year OS rates with dostarlimabwere 82.8% and 78.0%, respectively, and 57.5% and 46.0%, respectively, with placebo.

“These data confirm dostarlimab plus carboplatin/paclitaxel is a new standard-of-care for patients with primary advanced or recurrent endometrial cancer, regardless of their mismatch repair status,” said Matthew A. Powell, professor of obstetrics and gynecology, and chief in the Division of Gynecologic Oncology, at Washington University in St. Louis, in Missouri, in an oral presentation of the data during the SGO Meeting.

REFERENCES:

1. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. News release. FDA. August 1, 2024. Accessed August 1, 2024. https://tinyurl.com/mrxunh95

2. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. July 31, 2023. Accessed July 12, 2024. https://tinyurl.com/3uyucywe 

3. Powell MA, Auranen A, Willmott LJ, et al. Overall survival among patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy in the ENGOT-EN6-NSGO/GOG-3031/RUBY Trial. Presented at: Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.