Dostarlimab Combo Earns Expanded European Approval in Endometrial Cancer

Dostarlimab/chemotherapy elicited a 31% decrease in the risk of death compared with placebo/chemotherapy in locally advanced/recurrent endometrial cancer.

The European Commission (EC) has approved dostarlimab (Jemperli) plus chemotherapy in the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer who are also candidates for systemic therapy, according to a press release from the developer, GSK.¹

Previously the EC’s indication had the combination approved for patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) endometrial tumors.² In April 2024, dostarlimab plus chemotherapy received priority review from the FDA in all advanced endometrial cancers.³ In August 2024, the FDA granted approval to the combination for advanced/recurrent endometrial cancer.⁴

Supporting results came from part 1 of the double-blind, randomized, phase 3 RUBY trial (NCT03981796) that evaluated the efficacy and safety of dostarlimab plus chemotherapy followed by dostarlimab compared with placebo plus chemotherapy followed by placebo in patients with recurrent or primary advanced endometrial cancer.

“Clinicians have been waiting for years for an immuno-oncology–based option that can meaningfully improve overall survival outcomes for patients with MMRp/MSS primary advanced or recurrent endometrial cancer,” Mansoor Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, and the principal investigator of the RUBY trial, said in the press release.¹ “The expanded approval represents a significant advance that delivers on this hope, now for patients with both [deficient] MMR [dMMR]/MSI-[high] and MMRp/MSS tumors.”

When compared with chemotherapy alone, dostarlimab plus chemotherapy demonstrated a 31% reduction in the risk of death (HR, 0.69; 95% CI, 0.54-0.89).⁵

At 2.5 years, there was a 61% chance of survival (95% CI, 54%-67%) in the dostarlimab/chemotherapy group vs 49% (95% CI, 43%-55%) in the placebo/chemotherapy group. Median overall survival (OS) was 44.6 months (95% CI, 32.6-not reached [NR]) in the dostarlimab group vs 28.2 months (95% CI, 22.1-35.6) in the placebo group, a 16.4 month improvement in favor of dostarlimab. In the overall trial population, the median duration of follow-up was 37.2 months (range, 31.0-49.5).

The trial’s primary end points were progression-free survival per investigator assessment according to RECIST v1.1 in the dMMR/MSI-high and overall populations and OS in the overall population.

A total of 494 patients were randomly assigned, in a 1:1 ratio, to receive either 500 mg of dostarlimab (n = 245) or placebo (n = 249) intravenously with chemotherapy consisting of 5 mg/ml/minute area under the curve carboplatin and 175 mg/m² of body surface area of paclitaxel intravenously every 3 weeks for the first 6 cycles, then either 1000 mg of dostarlimab or placebo intravenously every 6 weeks for up to 3 years or until disease progression, treatment discontinuation due to toxicity, withdrawal, investigator’s decision to withdraw the patient, or death.

Patients were required to be 18 years or older with histologically or cytologically confirmed primary advanced (stage III or IV) or recurrent endometrial cancer who were not able to be cured by radiation therapy, surgery, or both. Additionally, patients were required to have one of the following criteria: primary advanced stage IIIA, IIIB, or IIIC1 disease measurable per RECIST v1.1 criteria; primary advanced stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histologic characteristics, regardless of measurable disease presence; initial recurrent disease without previous systemic therapy; or recurrent disease previously treated with neoadjuvant or adjuvant systemic therapy with recurrence or progression at least 6 months after treatment.

Regarding safety, the most common treatment-emergent adverse events (TEAEs) were fatigue (52.3% in the dostarlimab group vs 54.9% in the placebo group), alopecia (53.9% vs 50.0%, respectively), nausea (54.4% vs 46.3%), and neuropathy (44.0% vs 41.9%). The most common TEAEs of grade 3 or higher were anemia (14.9% vs 16.7%, respectively), neutropenia (9.5% vs 9.3%), and neutrophil count decreased (8.3% vs 13.8%). Serious TEAEs occurred in 39.8% of the dostarlimab group and 28.0% of the placebo group.

References

1. European Commission expands Jemperli (dostarlimab) plus chemotherapy approval to all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. January 20, 2025. Accessed January 20, 2025. https://tinyurl.com/y4nzn2ce
2. GSK’s Jemperli (dostarlimab) plus chemotherapy approved as the first and only frontline immuno-oncology treatment in the European Union for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. December 11, 2023. Accessed January 20, 2025. https://bit.ly/3NiI1mL
3. US FDA accepts for priority review GSK’s application for an expanded indication of Jemperli (dostarlimab) plus chemotherapy to include all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. April 24, 2024. Accessed January 20, 2025. https://tinyurl.com/msvnm4pp
4. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. News release. FDA. August 1, 2024. Accessed January 20, 2025. https://tinyurl.com/mtr6tpyp
5. Powell MA, Bjørge L, Willmott L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024;35(8):728-738. doi:10.1016/j.annonc.2024.05.546