Dostarlimab Plus Chemotherapy Combo Meets PFS End Point in Advanced or Recurrent Endometrial Cancer

The combination of dostarlimab-gxly (Jemperli) plus standard-of-care chemotherapy, followed by dostarlimab alone, produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy alone in patients with primary advanced or recurrent endometrial cancer, meeting the primary end point of the phase 3 RUBY trial (NCT03981796).¹

Findings from a planned interim analysis showed that the PFS benefit was observed in the prespecified mismatch repair deficient (dMMR)/microsatellite instability–high (MSI-H) patient subgroup and in the overall population. Additionally, a clinically relevant benefit in PFS was observed in the mismatch repair proficient (MMRp)/microsatellite stable (MSS) patient subgroup.

Although overall survival (OS) data were immature at the time of the interim analysis, a trend favoring the dostarlimab regimen was observed in the overall population, including the dMMr/MSI-H and MMRp/MSS subgroups.

Full results from the trial will be published in a medical journal and presented at an upcoming medical meeting. GSK intends to seek regulatory approvals for a potential new indication for dostarlimab in the treatment of primary advanced or recurrent endometrial cancer, and submission based on the results of RUBY are anticipated in the first half of 2023.

“Patients with primary advanced or recurrent endometrial cancer have limited treatment options. Long-term outcomes remain poor, and new treatment options are urgently needed to evolve the current standard of care, which is platinum-based chemotherapy,” Hesham Abdullah, senior vice president, global head of Oncology Development at GSK, stated in a press release. “Based on these positive headline results from the RUBY trial, GSK intends to seek regulatory approvals for a potential new indication for dostarlimab in the treatment of primary advanced or recurrent endometrial cancer.”

The 2-part global, randomized, double-blind, multicenter RUBY trial investigated the use of dostarlimab in patients with primary advanced or recurrent endometrial cancer. Part 1 examined dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab alone, compared with carboplatin and paclitaxel plus placebo, followed by placebo alone. In part 2, patients were administered dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab plus niraparib (Zejula), compared with carboplatin and paclitaxel plus placebo, followed by placebo alone.

To enroll in either part of the trial, patients were required to by at least 18 years of age with histologically or cytologically proven endometrial cancer with recurrent or advanced disease.² Stage III or IV disease or first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone was required. Patients also needed to have an ECOG performance status of 0 or 1 and adequate organ function.

Key exclusion criteria included patients who received neoadjuvant/adjuvant systemic anticancer therapy for primary stage III or IV disease and did not have a recurrence or progressive disease prior to first dose on the study or did have a recurrence or progressive disease within 6 months of completing systemic anticancer therapy treatment prior to first dose on the study; more than 1 recurrence of endometrial cancer prior anti–PD-(L)1 therapy; anticancer therapy within 21 days of study treatment; or uncontrolled central nervous system metastases or carcinomatosis meningitis.

The co-primary end points of part 1 was investigator-assessed PFS per RECIST v1.1 criteria and OS. Investigator-assessed PFS was the primary end point of part 2. Secondary end points for both parts of the trial include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, safety, and tolerability.

Regarding safety, the toxicity profile of dostarlimab in RUBY was consistent with clinical trials of similar regimens. The most common treatment-emergent adverse effects in patients receiving dostarlimab plus chemotherapy included nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, and diarrhea.

References

1. Jemperli (dostarlimab-gxly) RUBY phase III trial met its primary endpoint in a planned interim analysis in patients with primary advanced or recurrent endometrial cancer. News release. GSK. December 2, 2022. Accessed December 2, 2022. https://bit.ly/3H1XEgl
2. 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 August 12, 2022. Accessed December 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03981796