GSK plc announced that the U.S. Food and Drug Administration (FDA) granted approval for Jemperli (dostarlimab) in conjunction with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a standalone treatment for adult patients with primary advanced or recurrent endometrial cancer.
The new approval extends the previous indication of Jemperli combined with chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, which account for 70-75% of endometrial cancer cases and currently have limited treatment options.
The supplemental Biologics License Application (sBLA) for this expanded use received Priority Review and was approved before the Prescription Drug User Fee Act (PDUFA) action date.
Hesham Abdullah, GSK’s Senior Vice President and Global Head of Oncology R&D commented, “The approval of Jemperli plus chemotherapy as the first and only immuno-oncology regimen to demonstrate a significant overall survival benefit for adult patients with primary advanced or recurrent endometrial cancer, regardless of biomarker status, is a significant advancement. We are excited to offer this treatment option to a broader range of patients in the US, including the 70-75% with MMRp/MSS tumors who have had few options available to them”.
The expanded approval is based on data from the RUBY phase III trial’s Part 1, which showed significant improvements in both progression-free survival (PFS) and overall survival (OS). The RUBY Part 1 trial is the only study to date demonstrating a statistically significant OS benefit in patients with primary advanced or recurrent endometrial cancer, showing a 31% reduction in the risk of death (HR: 0.69; 95% CI: 0.54–0.89) when compared to chemotherapy alone.
At the 2.5-year mark, 61% of patients receiving Jemperli plus chemotherapy were alive compared to 49% in the chemotherapy-only group. The median OS was improved by 16.4 months 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 safety profile of Jemperli in combination with carboplatin-paclitaxel was consistent with the known safety profiles of the individual drugs, with common adverse effects including nausea, alopecia, fatigue, and peripheral neuropathy.
Dr. Matthew Powell, Chief of the Division of Gynaecologic Oncology at Washington University School of Medicine and US principal investigator for the RUBY trial noted, “The initial approval of Jemperli plus chemotherapy was a transformative moment for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. The expanded approval now provides a valuable new option for the larger patient population, demonstrating the only immuno-oncology treatment regimen with a statistically significant overall survival benefit”.
Adrienne Moore, President of the Endometrial Cancer Action Network for African-Americans (ECANA), expressed optimism about the expanded approval, stating, “This new treatment regimen offers hope to patients and their families, providing a much-needed option for those with advanced or recurrent endometrial cancer. Survivors and advocates should welcome this development as it expands treatment possibilities in the US.”
Endometrial cancer, which originates in the uterine lining, is the most common gynaecologic cancer in developed nations. With around 1.6 million people living with active disease and 417,000 new cases reported globally each year, the incidence is expected to rise by about 40% between 2020 and 2040. Approximately 15-20% of patients are diagnosed with advanced disease, and 70-75% of those with advanced or recurrent endometrial cancer have MMRp/MSS tumors.
The RUBY trial is an international, multi-part phase III study examining the efficacy of dostarlimab combined with carboplatin-paclitaxel followed by dostarlimab versus the same regimen plus placebo. Part 1 evaluates PFS and OS, including analyses of both MMRp/MSS and dMMR/MSI-H populations, while Part 2 explores the addition of niraparib. RUBY involves collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT) and the GOG Foundation.
Jemperli, a PD-1-blocking antibody, is central to GSK’s immuno-oncology research and development program, which includes studies in various cancers. In the US, Jemperli is approved for use in combination with chemotherapy and as a single agent for advanced endometrial cancer, including both MMRp/MSS and dMMR/MSI-H tumors, with ongoing studies to verify its clinical benefits in solid tumors.
As reported by pharmabiz.com, Jemperli was originally discovered by AnaptysBio, Inc., and licensed to Tesaro, Inc., with GSK now responsible for its research, development, and commercialization. GSK continues to focus on advancements in oncology, targeting haematologic malignancies, gynaecologic cancers, and other solid tumors through immuno-oncology and tumor-targeting therapies.