FDA Accepts sBLA of Dostarlimab/Chemo to Include All Advanced Endometrial Cancer

• A supplemental biologics license application (sBLA) for the combination of dostarlimab-gxly (Jemperli) with standard-of-care chemotherapy has been accepted by the FDA.
• This application is supported by data from the RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).
• This sBLA aims to expand the already approved combination to help all adult patients with primary advanced or recurrent endometrial cancer, including patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) tumors.

The FDA has accepted the sBLA for the combination of dostarlimab with standard-of-care chemotherapy, consisting of carboplatin and paclitaxel, to expand treatment to all adult patients with primary advanced or recurrent endometrial cancer, including those with pMMR/MSS tumors.¹

Findings from part 1 of the phase 3 RUBY trial showed statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) results, supporting this application. According to results presented during the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer, the combination elicited a 31% improvement in OS vs placebo/chemotherapy in patients with primary advanced or recurrent endometrial cancer, regardless of microsatellite instability (MSI) status.²

A Prescription Drug User Fee Act action date of August 23, 2024, has been assigned for the combination.¹

“[Dostarlimab] has become another tool we have in our armamentarium. Moving this to frontline therapy has been the big goal,” Matthew A. Powell, MD, Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology at Washington University School of Medicine in St. Louis, told Targeted Oncology^TM.

Matthew A. Powell, MD

At 51.2% maturity and a median follow-up of 37.2 months, the median OS with dostarlimab plus chemotherapy was 44.6 months (95% CI, 32.6-not estimated [NE]) vs 28.2 months (95% CI, 22.1-35.6) with placebo/chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; P = .002).² These data crossed the prespecified stopping boundary for OS (P = .01101) and were found to be statistically significant and clinically relevant. At 2 and 3 years, OS rates among those treated with dostarlimab were 70.1% and 54.9%, respectively, compared with 54.3% and 42.9% in the placebo arm.

At a median follow-up of 36.6 months in patients whose tumors were mismatch repair deficient (dMMR)/ MSI-high (MSI-H), the maturity rate was 39.8%. The median OS rates for these patients were NE (95% CI, NE-NE) with dostarlimab vs 31.4 months (95% CI, 20.3-NE) with placebo (HR, 0.32; 95% CI, 0.17-0.63). The 2- and 3-year OS rates were 82.8% and 78.0% with dostarlimab, respectively, and 57.5% and 46.0% with placebo.

In the pMMR/MSS subgroup at a median follow-up of 37.5 months, the median OS was 34.0 months (95% CI, 28.6-NE) with dostarlimab compared with 27.0 months (95% CI, 21.5-35.6) with placebo (HR, 0.79; 95% CI, 0.60-1.04). The OS maturity rate was 54.8%, and at 2 and 3 years, OS rates with dostarlimab were 66.5% and 48.6%, respectively, vs 53.2% and 41.9%, respectively, in the placebo arm.

3D illustration of uterus cancer and endometrial malignant tumor as a uterine medical concept © Crystal Light - stock.adobe.com

Previous interim findings of the study led the FDA to approve dostarlimab in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, in July 2023 for use in patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by an FDA-approved test, or MSI-H.

“This is transformative. Adding checkpoint inhibition to the upfront treatment for our patients with advanced/recurrent endometrial cancer is the standard of care,” added Powell.

About the Phase 3 RUBY Trial

The 2-part, global, randomized, double-blind, multicenter, phase 3 RUBY trial enrolled patients with primary advanced or recurrent endometrial cancer. In part 1, investigators enrolled 494 patients and evaluated dostarlimab plus carboplatin/paclitaxel followed by dostarlimab vs carboplatin/paclitaxel plus placebo followed by placebo. Part 2 of the trial is assessing dostarlimab plus carboplatin/paclitaxel followed by dostarlimab plus niraparib (Zejula) vs placebo plus carboplatin/paclitaxel followed by placebo.

Enrollment was open to patients with stage III/IV disease or first recurrent endometrial cancer, with all histologies permitted except sarcomas. Patients could either not have previously received systemic therapy or had disease recurrence or progression within 6 months after completion of systemic anticancer treatment.

Patients were stratified by MMR/MSI status, prior external pelvic radiation, and disease status.

The dual primary end points in part 1 are investigator-assessed PFS based on the RECIST v1.1 and OS. In Part 2, the primary end point is investigator-assessed PFS in the overall population and PFS in the pMMR and MSS population. OS in the overall population serves as a key secondary end point in the trial with additional secondary end points in both parts being PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

REFERENCES:

1. 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 plc. April 24, 2024. Accessed April 24, 2024. https://tinyurl.com/4sv84rbt

2. Powell MA, Auranen A, Willmott LJ, et al. Overall survival among patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy in the ENGOT-EN6-NSGO/GOG-3031/RUBY Trial. Presented at: Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.