FDA Expands Approval of Dostarlimab-Gxly Plus Chemotherapy to All Adults With Primary, Recurrent Endometrial Cancer

The FDA expanded the approval of dostarlimab-gxly (Jemperli; GlaxoSmithKline [GSK]) in combination with carboplatin and paclitaxel chemotherapy, followed by dostarlimab-gxly as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer, according to a news release.¹

Image credit: MdBabul | stock.adobe.com

Expansion of this approval broadens the previous indication for dostarlimab-gxly plus chemotherapy, now including patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, who represent 70% to 75% of patients diagnosed with endometrial cancer and have limited options for treatment.¹

“Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status,” Hesham Abdullah, MD, MSc, senior vice president and global head of oncology at GSK, said in the news release.¹

The FDA previously approved dostarlimab-gxly with chemotherapy for adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient as determined by an FDA-approved test.²

This approval was months after the approval of dostarlimab-gxly alone for the treatment of patients with endometrial cancer.³

Dostarlimab-gxly is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks it from interacting with PD-1 ligands. Through multiple clinical trials, the drug has shown potential as both a monotherapy and in combination with both standard of care and future developed cancer therapies.²

The expanded approval is based on results from the dual primary end points of progression-free survival (PFS) and overall survival (OS) from part 1 of the RUBY phase 3 trial. This trial demonstrated a 31% reduction in the risk of death (HR: 0.69; 95% CI, 0.54-0.89) compared to standalone chemotherapy.¹

At the 2.5-year follow-up point, 61% (95% CI, 54-67%) of patients in the dostarlimab-gxly plus chemotherapy group were alive, compared to 49% (95% CI: 43-55%) in the chemotherapy alone group. Additionally, there was a 16.4-month improvement in median OS observed with dostarlimab-gxly compared to just chemotherapy (44.6 months [95% CI, 32.6-NR] vs 28.2 months [95% CI: 22.1-35.6], respectively).¹

Safety profiles were generally consistent with the already-known safety profiles of individual agents. The most reported treatment-emergent adverse events—occurring in around 20% of participants—in patients receiving dostarlimab-gxly plus chemotherapy include nausea, fatigue, anemia, rash, vomiting, and others.¹

“This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer,” Matthew Powell, MD, chief of the gynecologic oncology division at Washington University and US principal investigator of the RUBY trial, said in the news release.¹

Endometrial cancer is the most common form of gynecologic cancer in developed countries, with 417,000 new cases reported worldwide yearly and an estimated 1.6 million people living with active disease at any stage. In addition, incidence rates are expected to rise by approximately 40% between 2020 and 2040.¹

Part 2 of the RUBY trial will assess PFS in the overall population, followed by PFS in the MMRp/MSS population.¹

References

1. BusinessWire. US FDA expands Jemperli (dostarlimab-gxly) plus chemotherapy approval to all adult patients with primary advanced or recurrent endometrial cancer as the first and only immuno-oncology-based treatment to show an overall survival benefit. News Release. Released August 1, 2024. Accessed August 1, 2024. https://www.businesswire.com/news/home/20240726127513/en/US-FDA-expands-Jemperli-dostarlimab-gxly-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer-as-the-first-and-only-immuno-oncology-based-treatment-to-show-an-overall-survival-benefit?_gl=1*10g7n52*_gcl_au*MTI5NDAzNDgwOC4xNzE3MDkzODY1LjEyNjc0NjU5NC4xNzE3MTg3MDc3LjE3MTcxODcwNzY.*_ga*MTk0Mjg0MjgyNC4xNjk5NjMwMTU3*_ga_ZQWF70T3FK*MTcyMjUzNzkxOC43MS4xLjE3MjI1NDE0NjAuNjAuMC4w

2. PT Staff. FDA approves dostarlimab combination for primary advanced or recurrent endometrial cancer. Pharmacy Times. Published August 1, 2023. Accessed August 1, 2024. https://www.pharmacytimes.com/view/fda-approves-dostarlimab-combination-for-primary-advanced-or-recurrent-endometrial-cancer

3. Antrim A. FDA approves dostarlimab-gxly for recurrent, advanced mismatch repair-deficient endometrial cancer. Pharmacy Times. Published February 10, 2023. Accessed August 1, 2024. https://www.pharmacytimes.com/view/fda-approves-dostarlimab-gxly-for-recurrent-advanced-mismatch-repair-deficient-endometrial-cancer