FDA Approves Expanded Indication for Dostarlimab Plus Chemo in Primary Advanced or Recurrent Endometrial Cancer

FDA

The FDA has approved dostarlimab-gxly (Jemperli) in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, for the treatment of adult patients with primary advanced or recurrent endometrial cancer.^1,2

Previously in July 2023, the regulatory agency approved the combination, followed by dostarlimab monotherapy, for use in adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability high (MSI-H).³

The expanded approval is supported by data from part 1 of the phase 3 RUBY trial (NCT03981796), which showed that in the overall population, patients treated with dostarlimab plus chemotherapy (n = 245) experienced a statistically significant improvement in overall survival (OS) compared with those treated with placebo plus chemotherapy (n = 249; HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002). The median OS was 44.6 months (95% CI, 32.6–not reached [NR]) in the dostarlimab arm vs 28.2 months (95% CI, 22.1-35.6) in the placebo arm.^1,4

The median progression-free survival (PFS) was 11.8 months (95% CI, 9.6-17.1) in the dostarlimab arm vs 7.9 months (95% CI, 7.6-9.5) in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; 1-sided P < .0001).

"The initial approval of [dostarlimab] plus chemotherapy was practice changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, and today’s expanded approval will offer even more patients the opportunity for improved outcomes," Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine in St. Louis, Missouri, and United States principal investigator of the RUBY trial, stated in a news release.² “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer."

Part 1 of the multicenter, randomized, double-blind, placebo-controlled RUBY trial, enrolled patients at least 18 years of age with histologically or cytologically proven endometrial cancer. Specifically, patients needed to have primary stage IIIA to IIIC1 endometrial cancer with evaluable or measurable disease per RECIST 1.1 criteria according to investigator assessment; primary stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histology with or without evaluable or measurable disease; primary stage IIIC2 or IV disease irrespective of evaluable or measurable disease status; first recurrent disease naive to systemic anticancer therapy; or recurrent or progressive disease at least 6 months following prior neoadjuvant or adjuvant systemic anticancer therapy.⁵

All patients were required to have adequate organ function and an ECOG performance status of 0 or 1.

Patients in part 1 were randomly assigned to receive dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab monotherapy; or placebo plus carboplatin and paclitaxel, followed by placebo monotherapy.

Investigator-assessed PFS and OS served as the trial's coprimary end points. Secondary end points included PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, time to second progression, and safety.

Additional data showed that in the subset of patients with mismatch repair–proficient/microsatellite stable disease, those treated with the dostarlimab regimen (n = 192) achieved a median OS of 34.0 months (95% CI, 28.6-NR) vs 27.0 months (95% CI, 21.5-35.6) for those given the placebo regimen (HR, 0.79; 95% CI, 0.602-1.044).⁴

In patients with dMMR/MSI-H disease, the median OS was NR (95% CI, NR-NR) in the dostarlimab arm (n = 53) compared with 31.4 months (95% CI, 20.3-NR) in the placebo arm (n = 65; HR, 0.32; 95% CI, 0.166-0.629).

Regarding safety, the most common adverse effects reported in at least 20% of all patients in the dostarlimab arm included anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection and vomiting.¹

Dostarlimab is recommended at a dose of 500 mg once every 3 weeks for 6 cycles in combination with carboplatin and paclitaxel, followed by 1000 mg as a single agent once every 6 weeks for up to 3 years or until disease progression or unacceptable toxicity. Patients should be treated with dostarlimab before chemotherapy when given on the same day.

References

1. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed August 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
2. US FDA expands Jemperli (dostarlimab) plus chemotherapy approval to all adult patients with primary advanced or recurrent endometrial cancer as the first and only immuno-oncology-based treatment to show an overall survival benefit. News release. GSK. August 1, 2024. Accessed August 1, 2024. https://www.gsk.com/en-gb/media/press-releases/us-fda-expands-jemperli-dostarlimab-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/
3. FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer. FDA. July 31, 2023. Accessed August 1, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-dostarlimab-gxly-chemotherapy-endometrial-cancer
4. 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://www.gsk.com/en-gb/media/press-releases/positive-ruby-phase-iii-data-show-potential-for-jemperli-dostarlimab-combinations-in-more-patients-with-primary-advanced-or-recurrent-endometrial-cancer
5. 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. Updated May 17, 2024. Accessed August 1, 2024. https://clinicaltrials.gov/study/NCT03981796