GSK's PD-1 Inhibitor Jemperli Receives FDA Priority Review for First-Line Treatment of dMMR/MSI-H Advanced or Recurrent Endometrial Cancer

On June 6, GSK announced that the supplemental Biologics License Application (sBLA) for its PD-1 monoclonal antibody Jemperli (dostarlimab) has been accepted by the FDA for priority review, with a PDUFA date set for September 23, 2023. The indication applied for is in combination with chemotherapy as a first-line treatment for adult patients with primary advanced or recurrent endometrial cancer characterized by mismatch repair deficiency (dMMR) / high microsatellite instability (MSI-H). If approved, this product is expected to become the first first-line therapy in the field of endometrial cancer in decades.

This sBLA is primarily based on the positive results of the Phase III RUBY study. The study is a global, multicenter, randomized, double-blind, placebo-controlled clinical trial (N=785), consisting of Part 1 and Part 2. These parts aim to evaluate the efficacy and safety in patients with primary advanced (Stage III or IV) or recurrent endometrial cancer: ① receiving dostarlimab combined with carboplatin and paclitaxel followed by dostarlimab monotherapy vs. receiving placebo combined with carboplatin and paclitaxel followed by placebo monotherapy; ② receiving dostarlimab combined with carboplatin and paclitaxel followed by dostarlimab combined with niraparib vs. receiving placebo combined with carboplatin and paclitaxel followed by placebo monotherapy.

The primary endpoints of Part 1 are progression-free survival (PFS) and overall survival (OS), while the primary endpoint of Part 2 is PFS.

Data showed that in the overall population (N=494), the risk of disease progression and death was reduced by 36% in the dostarlimab group; the 2-year PFS rate was 36.1% in the dostarlimab group versus 18.1% in the placebo group; the 2-year OS rate was 71.3% in the dostarlimab group versus 56.0% in the placebo group.

Source: NEJM

In the subgroup of patients with mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H) (N=118), the risk of disease progression and death in the dostarlimab group was reduced by 72% and 70%, respectively; the 2-year PFS rate was 61.4% in the dostarlimab group and 15.7% in the placebo group; the 2-year OS rate was 83.3% in the dostarlimab group and 58.7% in the placebo group.

Source: N EJM

Endometrial cancer is the most common gynecological cancer in developed countries, with approximately 417,000 confirmed cases globally each year. About 15%-20% of patients with endometrial cancer are diagnosed at an advanced stage, and 20%-29% of patients have dMMR/MSI-H. The current standard first-line treatment for this disease is carboplatin combined with paclitaxel. However, unfortunately, the median OS for patients does not exceed three years.

Currently, only two biologics, dostarlimab and pembrolizumab, have been approved globally for second-line treatment of endometrial cancer. The former was approved in 2021, and the latter in 2019. Notably, in terms of first-line treatment for endometrial cancer, dostarlimab and pembrolizumab also lead the progress (see: ). Additionally, AstraZeneca's durvalumab has recently successfully completed a Phase III study for first-line treatment of endometrial cancer (see: ). Patients with endometrial cancer are expected to have more options for first-line treatment.

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