Dostarlimab/Chemo Improves Long-Term DOR in Advanced Endometrial Cancer

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Dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel led to a 4.4-month increase in median duration of response (DOR) vs placebo plus carboplatin and paclitaxel in patients with primary advanced or recurrent endometrial cancer, according to updated findings from the second interim analysis of part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796).1

The data, which were presented at the 2025 SGO Annual Meeting on Women’s Cancer, showed that in the overall trial population (n = 494), at a median follow-up of 37.2 months and a data cutoff of September 22, 2023, the overall response rates (ORRs) in the dostarlimab (n = 245) and placebo (n = 249) arms were 61.2% and 57.0%, respectively. With DOR data at 69.9% maturity, the median DOR was 10.6 months (95% CI, 8.2-18.4) in the dostarlimab arm vs 6.2 months (95% CI, 4.4-6.7) in the placebo arm. Patients in the dostarlimab arm had a 2.6-fold increased chance of achieving a DOR lasting at least 24 months vs those in the placebo arm (30.7% vs 12.0%). The 24-month DOR rates were 37.0% (95% CI, 28.8%-45.3%) and 14.3% (95% CI, 8.9%-20.9%), respectively.

“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.

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’s Current Role 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.

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.

References

1. Mirza MR, Willmott LJ, Hietanen S, et al. Updated duration of response for patients receiving dostarlimab plus carboplatin-paclitaxel treatment compared with patients receiving placebo plus carboplatin-paclitaxel in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. Presented at: 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, Washington. Poster 232.
2. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed March 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy