Source – GSK
GSK has secured approval from the US for Jemperli, in combination with chemotherapy, as a first-line treatment for previously untreated, primary advanced, or recurrent endometrial cancer. This makes Jemperli the first immunotherapy option approved for first-line use in these patients.
While GSK has achieved approval in a niche that could potentially help Jemperli become a blockbuster with over $1 billion in sales, the label agreed upon with the FDA is narrower than originally anticipated. The drug has been cleared for patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) deficiency mutations, even though the clinical trial, RUBY, demonstrated benefits across all patient populations.
According to GSK’s estimations, there are approximately 60,000 new cases of endometrial cancer diagnosed each year in the US, with 15% to 20% of them classified as advanced or metastatic. Among these cases, 20% to 29% are identified as dMMR or MSI-H.
The FDA has approved the use of Jemperli in combination with the standard first-line chemotherapy for endometrial cancer, consisting of carboplatin and paclitaxel. Subsequently, Jemperli can be used as a standalone therapy.
“As a clinician, I celebrate the practice-changing potential of adding Jemperli to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options. Based on the results from the RUBY clinical trial, I look forward to the addition of Jemperli to chemotherapy becoming a new standard of care for patients.”
– Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial
In the RUBY trial, adding Jemperli, a PD-1 inhibitor, to chemotherapy resulted in a 71% reduction in the risk of disease progression or death for patients with dMMR and MSI-H, leading to significant praise from principal investigator Matthew Powell of Washington University School of Medicine.
While GSK’s drug demonstrated a lower 24% reduction in patients without these biomarkers (pMMR or MSS), the approval signifies a race victory against MSD to secure a PD-1 inhibitor for front-line endometrial cancer treatment. MSD has reported similar data from its pivotal NRG-GY018 study of Keytruda (pembrolizumab), but no regulatory filing has been disclosed yet.
Both Jemperli and Keytruda had previously received approvals as monotherapies for second-line or later endometrial cancer treatments. However, approval in the first-line setting broadens the eligible patient population significantly.
GSK is closely monitoring the patients from the RUBY trial to assess if overall survival data can support an all-comer label in the future. Additionally, the study’s second phase is exploring the addition of GSK’s PARP inhibitor, Zejula (niraparib), to Jemperli after the initial Jemperli/chemo regimen, with results expected next year.
AstraZeneca may also pose as a potential competitor, as its PD-L1 inhibitor, Imfinzi (durvalumab), has shown promise in improving progression-free survival when used alone or with PARP inhibitor Lynparza (olaparib) in addition to chemotherapy for newly diagnosed advanced or recurrent endometrial cancer in the DUO-E study.
