Dostarlimab Shows Response in Endometrial Cancer

Wahner,Ashling;

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Dostarlimab Shows Response in Endometrial Cancer

May 14, 2025

By Ashling Wahner

Fact checked by Tony Berberabe, MPH

Publication

Article

Targeted Therapies in OncologyMay I, 2025

Volume 14

Issue 6

Pages: 47

Mansoor Raza Mirza, MD

Chief Oncologist

Department of Oncology

Rigshospitalet

Copenhagen University Hospital

Medical Director

Nordic Society of Gynaecologic

Oncology-Clinical Trial Unit (NSGOCTU)

Copenhagen, Denmark

Updated results from the phase 3 ENGOT-EN6-NSGO/GOG3031/RUBY study (NCT03981796) show that adding dostarlimab-gxly (Jemperli) to standard chemotherapy significantly improves the median duration of response (DOR) by 4.4 months compared with chemotherapy alone in patients with primary advanced or recurrent endometrial cancer. The findings from the second interim analysis of part 1 reinforce the potential of this immunotherapy-chemotherapy combination.¹

At the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, investigators reported that among 494 patients (median follow-up, 37.2 months; data cutoff, September 22, 2023), the dostarlimab arm (n = 245) achieved an overall response rate (ORR) of 61.2%, compared with 57.0% in the placebo arm (n = 249).

With DOR data 69.9% mature, the median DOR was significantly longer with dostarlimab—10.6 months (95% CI, 8.2-18.4) vs 6.2 months (95% CI, 4.4-6.7) with placebo. Patients receiving dostarlimab were 2.6 times more likely to maintain a response for at least 24 months (30.7% vs 12.0%). The 24-month DOR rates further underscored this benefit: 37.0% (95% CI, 28.8%-45.3%) in the dostarlimab arm vs 14.3% (95% CI, 8.9%-20.9%) in the placebo arm.

“The substantial improvement in DOR [with dostarlimab vs placebo] was seen in all 3 populations, including the mismatch repair–proficient [pMMR]/microsatellite-stable [MSS] population, in which [the] median DOR was increased by 1.4 times,” lead study author Mansoor Raza Mirza, MD, and coauthors wrote in the poster. Mirza is chief oncologist at the Department of Oncology at Rigshospitalet, Copenhagen University Hospital, in Denmark.

In the pMMR/MSS population, the ORRs in the dostarlimab (n = 192) and placebo (n = 184) arms were 57.8% and 55.4%, respectively. The median DOR was 8.6 months (95% CI, 6.9-13.1) in the dostarlimab arm vs 6.3 months (95% CI, 4.4-7.1) in the placebo arm. The probability of having a DOR lasting at least 24 months was 22.5% in the dostarlimab arm vs 12.7% in the placebo arm. The 24-month DOR rates were 27.6% (95% CI, 19.0%-36.8%) and 14.7% (95% CI, 8.4%-22.7%), respectively.

Cancer cell image by Gwendolyn Salas / MJH Life Sciences using AI

In the MMR-deficient [dMMR]/microsatellite instability–high [MSI-H] population, the ORRs in the dostarlimab (n = 53) and placebo (n = 65) arms were 73.6% and 61.5%, respectively. The median DOR was not reached (NR; 95% CI, 10.1 months-NR) in the dostarlimab arm vs 5.4 months (95% CI, 3.9-8.1) in the placebo arm. Patients in the dostarlimab arm had a 5.4-fold increased chance of achieving a DOR lasting at least 24 months; this rate was 53.8% in the dostarlimab arm vs 10.0% in the placebo arm. The 24-month DOR rates were 62.2% (95% CI, 44.5%-75.6%) and 13.2% (95% CI, 4.6%-26.3%), respectively.

Dostarlimab in Advanced/Recurrent Endometrial Cancer

In August 2024, the FDA approved dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab monotherapy, for the treatment of adult patients with primary advanced or recurrent endometrial cancer, regardless of MMR/MSS status.² This regulatory decision was based on data from RUBY part 1, in which patients in the overall population who received dostarlimab plus chemotherapy achieved a median overall survival (OS) of 44.6 months (95% CI, 32.6-NR) vs 28.2 months (95% CI, 22.1-35.6) among those who received placebo plus chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002). The median progression-free survival (PFS) in these respective populations was 11.8 months (95% CI, 9.6-17.1) and 7.9 months (95% CI, 7.6-9.5; HR, 0.64 [95% CI, 0.51-0.80; 1-sided P < .0001]).

RUBY Part 1 Trial Design

Part 1 of the randomized, double-blind, multicenter RUBY trial randomly assigned patients with primary advanced or recurrent endometrial cancer to receive 500 mg of dostarlimab or placebo in combination with carboplatin and paclitaxel every 2 weeks for 6 cycles, followed by 1000 mg of dostarlimab or placebo monotherapy every 6 weeks for a maximum of 3 years or until progressive disease, toxicity, withdrawal of consent, investigator’s decision, or death (whichever occurred first).¹

The primary end points were investigator-assessed PFS per RECIST 1.1 criteria in both the dMMR/MSI-H and overall populations, as well as OS in the overall population. Investigator-assessed DOR per RECIST 1.1 criteria in the pMMR/MSS population was a prespecified exploratory end point.

ilham (uterus) - stock.adobe.com

Updated Safety Data and Next Steps

Few patients in the overall, pMMR/ MSS, and dMMR/MSI-H populations experienced dostarlimab or placebo-related immune-related adverse effects (AEs) after 24 months of treatment. In the overall population, the most common dostarlimab-related immune-related AEs were hypothyroidism (year 1, 10.4%; year 2, 4.6%; year 3, 0%; year 4, 0%), arthralgia (4.1%; 4.6%; 1.9%; 5.9%), rash (6.6%; 0%; 1.9%; 0%), and increased alanine aminotransferase (ALT) levels (5.4%; 1.1%; 1.9%; 0%).

In the pMMR/MSS population, the most common dostarlimab-related immune- related AEs were hypothyroidism (10.1%; 3.3%; 0%; 0%), arthralgia (3.2%; 6.7%; 0%; 0%), rash (6.3%; 0%; 3.3%; 0%), and increased ALT levels (5.3%; 1.7%; 0%; 0%).

In the dMMR/MSI-H population, the most common dostarlimab-related immune-related AEs were hypothyroidism (11.5%; 7.4%; 0%; 0%), arthralgia (7.7%; 0%; 4.3%; 16.7%), rash (7.7%; 0%; 0%; 0%), increased ALT levels (5.8%; 0%; 4.3%; 0%), maculopapular rash (3.8%; 3.7%; 4.3%; 0%), and hyperthyroidism (3.8%; 3.7%; 0%; 0%).

“These longer-term (> 3-year) follow-up data further support frontline use of dostarlimab plus carboplatin and paclitaxel as standard of care in all patients with primary advanced or recurrent endometrial cancer,” the authors concluded in the poster.