Dostarlimab Plus Chemo Earns Positive CHMP Opinion for Expanded Indication in Advanced Endometrial Cancer

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of an expanded indication for dostarlimab (Jemperli) in combination with carboplatin and paclitaxel for first-line treatment of all adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy.¹

In December 2023, the European Commission (EC) granted marketing authorization to dostarlimab plus carboplatin and paclitaxel for adult patients with mismatch repair­–deficient (dMMR)/microsatellite instability–high (MSI-H) primary advanced or recurrent endometrial cancer who are eligible to receive systemic treatment.² Under the CHMP’s recommendation, the approval would be expanded to include patients with mismatch repair–proficient (pMMR)/microsatellite stable (MSS) tumors, which account for approximately 70% to 75% of patients with endometrial cancer.¹

A final decision by the EC on the expanded marketing authorization is anticipated in the first quarter of 2025.

Both the initial approval and the application for the expanded indication were supported by data from part 1 of the phase 3 RUBY trial (NCT03981796), which demonstrated that patients in the overall population treated with dostarlimab plus chemotherapy (n = 245) experienced a median overall survival (OS) of 44.6 months vs 28.2 months for those given placebo plus chemotherapy (n = 245; HR, 0.69; 95% CI, 0.54-0.89; P = .0020).³The 24-month OS rates were 70.1% (95% CI, 63.8%-75.5%) and 54.3% (95% CI, 47.8%-60.3%), respectively.

In the dMMR/MSI-H population, the median OS was not reached in the dostarlimab arm (n = 53) compared with 31.4 months for the placebo arm (n = 65; HR, 0.32; 95% CI, 0.17-0.63; P = .0002). In the pMMR/MSS population, the median OS was 34.0 months for the dostarlimab arm (n = 192) vs 27.0 months for the placebo arm (n = 184; HR, 0.79; 95% CI, 0.60-1.04; P = .0493).

Previously reported data from part 1 of RUBY showed that the dostarlimab regimen produced statistically significant improvements in progression-free survival (PFS) in both the overall population (HR, 0.64; 95% CI, 0.51-0.80; P < .0001) and the dMMR/MSI-H population (HR, 0.28; 95% CI, 0.16-0.50). These findings supported the initial EC approval in the dMMR/MSI-H population.

In August 2024, the FDA approved dostarlimab-gxly in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, for the treatment of adult patients with primary advanced or recurrent endometrial cancer.⁴ The decision expanded on the July 2023 FDA approval of dostarlimab plus chemotherapy, which was limited to patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer.⁵

Findings from RUBY also supported both FDA decisions. The randomized, double-blind, multicenter trial enrolled patients at least 18 years of age with histologically or cytologically confirmed primary advanced FIGO stage III/IV or recurrent endometrial cancer that was not amenable to cure by radiation therapy and/or surgery.³

Patients were randomly assigned 1:1 to receive dostarlimab at 500 mg or placebo once every 3 weeks plus carboplatin at area under the curve of 5 mg/ml per minute and paclitaxel at 175 mg/m² once every 3 weeks for the first 6 cycles, followed by dostarlimab at 1000 mg or placebo once every 6 weeks for up to 3 years or until disease progression, adverse effects leading to treatment discontinuation, patient withdrawal, investigator’s decision, or death. Patients were stratified by MMR/MSI status, prior external pelvic radiation status, and disease status.

PFS in the dMMR/MSI-H and overall populations, as well as OS in the overall population, served as the trial’s primary end points. OS in the dMMR/MSI-H and pMMR/MSS populations was an exploratory end point.

Safety data from RUBY was showed that the profile of dostarlimab plus chemotherapy was consistent with the known safety profiles of each individual component.¹

References

1. Jemperli (dostarlimab) plus chemotherapy receives positive CHMP opinion to expand approval to all adult patients with primary advanced or recurrent endometrial cancer. GSK. December 16, 2024. Accessed December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-plus-chemotherapy-receives-positive-chmp-opinion-to-expand-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/
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 December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-as-the-first-and-only-frontline-immuno-oncology-treatment-in-the-european-union/
3. 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
4. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed December 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
5. 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 December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/