FDA Approves Expanded Use of Dostarlimab for Treatment of Endometrial Cancers

The FDA has expanded approval for dostarlimab (Jemperli) with chemotherapy for all adults with primary advanced or recurrent endometrial cancer. This treatment, now including patients with MMRp/MSS tumors, has shown a 31% reduction in death risk and significant improvements in survival rates.

GSK announced that the US Food and Drug Administration (FDA) has granted an expanded approval for PD-1 inhibitor dostarlimab (Jemperli), combined with chemotherapy, for treating all adults with primary advanced or recurrent endometrial cancer. This makes dostarlimab the first and only treatment in the immuno-oncology field proven to significantly enhance survival rates among this patient group.

Hesham Abdullah, Senior VP, 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.”

Dostarlimab is now approved in conjunction with carboplatin and paclitaxel, followed by solo dostarlimab therapy. Previously restricted to certain genetic profiles, its use is now extended to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, which account for 70-75% of endometrial cancer diagnoses.

Clinically Meaningful Improvements

The decision follows compelling results from the RUBY phase III trial, revealing a 31% reduction in death risk when using dostarlimab plus chemotherapy compared to chemotherapy alone. At the 2.5-year mark, 61% of patients receiving dostarlimab were still alive, versus 49% receiving chemotherapy only. This equates to a 16.4-month increase in median overall survival.

This expanded indication, supported by a supplemental Biologics License Application (sBLA), received Priority Review and was approved before the scheduled Prescription Drug User Fee Act action date.

Dr. Matthew Powell, Chief, Division of Gynecologic Oncology, and US principal investigator of the RUBY trial said: “The initial approval of Jemperli plus chemotherapy was practice-changing for patients. 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.”

Understanding Jemperli

Jemperli operates by blocking the PD-1 pathway, a mechanism cancer cells exploit to evade the immune system. GSK's robust research program continues to explore its effectiveness alone and in combination with other therapies across various cancers, including gynecological and colorectal cancers.

The safety and tolerability 

The safety analysis of RUBY Part 1 indicated that the combination of Jemperli and carboplatin-paclitaxel maintained a safety profile similar to that of the individual drugs. Common adverse events affecting over 20% of patients included nausea, alopecia, fatigue, various types of neuropathy, anemia, joint pain, constipation, diarrhea, muscle pain, rash, hypomagnesemia, reduced appetite, and vomiting.

Endometrial cancer, the most common type of uterine cancer, has been historically challenging to treat in its advanced stages. The expanded approval of Jemperli represents a critical development in oncology, promising enhanced treatment efficacy and expanded hope for patients.