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.- GSK

This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumours where treatment options have been limited.”

This expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone. At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.

The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (greater than 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation, diarrhoea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.

Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: “The initial approval of Jemperli 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. 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.”