FDA Expands Approval for Dostarlimab/Chemo in Advanced Endometrial Cancer

The FDA previously approved dostarlimab/chemotherapy for those with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) disease in July 2023.

The FDA has expanded approval status for dostarlimab-gxly (Jemperli) plus carboplatin/paclitaxel followed by single-agent dostarlimab to include all adult patients with primary advanced or recurrent endometrial cancer, according to a news release from the agency.¹

The FDA previously approved dostarlimab/chemotherapy for those with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) disease in July 2023.²

Supporting data for the expanded approval came from the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796). Topline data showed that the median overall survival (OS) with dostarlimab/chemotherapy was 44.6 months (95%CI, 32.6-not reached [NR]) vs 28.2 months (95% CI, 22.1-35.6) with placebo/chemotherapy across the overall population (HR, 0.69; 95% CI, 0.54-0.89; P = .002). Additionally, the median progression-free survival (PFS) in the overall population was 11.8 months (95% CI, 9.6-17.1) and 7.9 months (95% CI, 7.6-9.5) in each respective arm (HR, 0.64; 95% CI, 0.51-0.80; P <.0001).

Common adverse effects (AEs) that occurred in at least 20% of the dostarlimab arm included anemia, creatinine increases, peripheral neuropathy, white blood cell count decreases, fatigue, nausea, glucose increases, low platelet counts, lymphocytopenia, and neutropenia.

“RUBY part 1 is the first clinical trial to show a statistically significant and clinically meaningful improvement in [OS] for an immuno-oncology therapy in combination with chemotherapy in the overall population of patients with primary advanced or recurrent endometrial cancer,” lead investigator Matthew Powell, MD, the Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology Washington University School of Medicine in St. Louis, said in a press release on findings from part 1 of the RUBY trial, which he subsequently presented at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer.³ “As a clinician, I celebrate the results of the RUBY part 1 trial presented today, which show how dostarlimab added to chemotherapy could potentially benefit a broader set of patients with this type of cancer.”

Investigators of the global, double-blind, phase 3 RUBY trial assessed a total of 494 patients with primary advanced or recurrent endometrial cancer across 2 parts. In part 1, patients were assigned to receive dostarlimab or matched placebo plus carboplatin/paclitaxel followed by dostarlimab or placebo. In part 2, investigators evaluated dostarlimab plus chemotherapy followed by dostarlimab and niraparib (Zejula) compared with placebo in combination with chemotherapy.

Based on the RUBY trial, the recommended dose for dostarlimab in this indication is 500 mg every 3 weeks for 6 cycles plus carboplatin and paclitaxel followed by dostarlimab monotherapy at 1000 mg every 6 weeks. Treatment should continue for a maximum of 3 years or until progressive disease or unacceptable toxicity.

The trial’s primary end points were PFS per investigator assessment in the dMMR/MSI-H and overall populations as well OS in the overall population.

Patients 18 years and older with histologically or cytologically confirmed advanced or recurrent endometrial cancer and stage III or IV disease were able to enroll on the trial.⁴ Additional eligibility criteria included having an ECOG performance status of 0 or 1 and adequate organ function.

Those who had more than 1 event of recurrence of endometrial cancer or prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent were ineligible for enrollment. Patients were also unsuitable for study entry if they had uncontrolled central nervous system metastases, a concomitant malignancy, or unresolved adverse effects or complications following any prior major surgery.

References

1. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. News release. FDA. August 1, 2024. Accessed August 1, 2024. https://tinyurl.com/mtr6tpyp
2. 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 August 1, 2024. https://shorturl.at/izGL9
3. Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in more patients with primary advanced or recurrent endometrial cancer. News release. GSK. March 16, 2024. Accessed August 1, 2024. https://tinyurl.com/bduurwmp
4. A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). ClinicalTrials.gov. Accessed August 1, 2024. https://tinyurl.com/2bphnvpv