GSK secures expanded approval for Jemperli from FDA: A major advancement in endometrial cancer treatment

In a landmark decision, the US Food and Drug Administration (FDA) has extended its approval of Jemperli (dostarlimab) to include all adult patients with primary advanced or recurrent endometrial cancer. This expanded approval now encompasses patients with mismatch repair proficient (MMRp) or microsatellite stable (MSS) tumours, which account for the majority of endometrial cancer cases. This makes Jemperli, developed by GSK plc, the first immuno-oncology treatment to show a significant overall survival benefit for this broad patient group.

Expanded Approval Details

Jemperli, used in combination with carboplatin and paclitaxel, followed by Jemperli alone, has demonstrated a 31% reduction in the risk of death compared to chemotherapy alone. This pivotal expansion follows the results of Part 1 of the RUBY phase III trial, which is the only clinical study to show a statistically significant improvement in overall survival (OS) in patients with primary advanced or recurrent endometrial cancer. The trial revealed that Jemperli combined with chemotherapy leads to a 16.4-month increase in median OS compared to chemotherapy alone.

Significance of the New Approval

Hesham Abdullah, Senior Vice President and Global Head of Oncology Research & Development at GSK, praised the expanded approval, noting that Jemperli in combination with chemotherapy is the first and only immuno-oncology regimen to show a meaningful survival improvement across all patients with advanced or recurrent endometrial cancer, regardless of their biomarker status. This advancement is crucial for the 70-75% of patients with MMRp/MSS tumours who previously had limited treatment options.

Dr. Matthew Powell, Chief of the Division of Gynecologic Oncology at Washington University School of Medicine and US principal investigator of the RUBY trial, highlighted that this expanded approval offers a significant advancement in treatment, providing a valuable new option for a broader patient population. Adrienne Moore, President of the Endometrial Cancer Action Network for African-Americans, welcomed the approval, emphasizing the hope it brings to patients and their families by offering a new, potentially life-extending treatment.

Insights from the RUBY Trial

The RUBY trial, a global, randomised, double-blind, multicentre phase III study, is divided into two parts. Part 1 evaluates the efficacy of Jemperli combined with carboplatin and paclitaxel, followed by Jemperli alone, versus a similar regimen with placebo. Part 2 assesses the addition of niraparib to the Jemperli regimen. This trial aims to measure progression-free survival (PFS) and overall survival (OS) in patients with various tumour types, including MMRp/MSS and dMMR/MSI-H tumours.

About Jemperli

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody and a cornerstone of GSK’s immuno-oncology research. Discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., Jemperli is now managed by GSK. It is approved in the US for treating both MMRp/MSS and dMMR/MSI-H endometrial cancers, as well as recurrent or advanced solid tumours under accelerated approval. Continued approval for these indications will depend on further clinical validation.

What is the significance of the FDA’s expanded approval of Jemperli?

The FDA’s decision is particularly meaningful as it broadens the use of Jemperli to include all adult patients with advanced or recurrent endometrial cancer, not just those with specific genetic markers. This makes Jemperli the first immuno-oncology treatment to show a significant overall survival benefit for a broad patient group, including those with MMRp/MSS tumors, which constitute the majority of endometrial cancer cases​.

How does Jemperli work, and what are its benefits?

Jemperli is a PD-1-blocking antibody that enhances the body’s immune response against cancer cells. The drug has shown not only to improve survival rates but also to offer a new treatment option for patients with endometrial cancer that have limited choices due to their biomarker status​.

What were the results of the RUBY trial that led to this expanded approval?

In the RUBY trial, Jemperli combined with chemotherapy led to a 16.4-month increase in median overall survival compared to chemotherapy alone. This trial is the only clinical study to date that has shown such a statistically significant improvement in survival for patients with primary advanced or recurrent endometrial cancer​.

Are there any notable side effects associated with Jemperli?

Yes, common side effects include anemia, increased creatinine, peripheral neuropathy, among others. It is also associated with severe immune-mediated reactions which can affect any organ system. Such adverse effects necessitate close monitoring and management during treatment​.