FDA Approves GSK’s Jemperli for Endometrial Cancer

 

The U.S. Food and Drug Administration (FDA) approved GlaxoSmithKline’s new checkpoint inhibitor, Jemperli (dostarlimab), for patients with recurrent or advanced endometrial cancer. The approval was specifically for patients with recurrent or advanced endometrial cancer who had progressed on or after previous treatment with platinum-based chemotherapy and whose cancers have a dMMR genetic anomaly.

Two months ago, on February 25, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) granted a positive recommendation for the drug for the same indication. Jemperli is an infusion. The active component is dostarlimab, an antineoplastic monoclonal antibody that improves T-cell responses, including anti-tumor responses via blockade of PD-1 binding to PD-L1 and PD-L2 ligands.

Although PD-1/PD-L1 checkpoint inhibitors is becoming something of a crowded market, very few of them are approved for use in endometrial cancer.

GSK picked up the drug when it acquired Tesaro for $5.1 billion in 2019. Tesaro had a marketed drug, Zejula (niraparib) for ovarian cancer. In addition to Zejula and dostarlimab, Tesaro had a couple other oncology assets, including antibodies against ITM-3 and LAG-3.

“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the agency’s Center for Drug Evaluation and Research. “This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population.”

About three-quarters of endometrial cancers are diagnosed at an early stage and can be cured via surgery. However, in advanced and recurrent endometrial cancer, there are fewer therapeutic options after front-line treatment with platinum-based chemotherapy. About 25% to 30% of advanced endometrial cancer patients have dMMR mutations. dMMR stands for deficient MisMatch Repair. It is often associated with MSI-H, which stands for High levels of MicroSatellite Instability. MSI-H/dMMR can happen when a cell cannot repair mistakes made during cell division. MSI-H/dMMR is associated with different kinds of cancers and can be identified via specific FDA-approved tests.

The Jemperli approval came about via the FDA’s Accelerated Approval pathway. The drug had also received Priority Review and Breakthrough Therapy designations for this indication. Additional clinical trials may be needed to verify and describe expected clinical benefits of the drug and GSK is currently running those trials in more patients with dMMR endometrial tumors.

In January, GSK presented positive and updated data from GARNET cohort F of dostarlimab in dMMR non-endometrial advanced solid cancers at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). The data demonstrated a 38.7% objective response rate (ORR) in patients with dMMR advanced solid cancers who received the drug. After a median follow-up of 12.4 months, the median duration of response (DoR) hadn’t been reached and the responses were durable across tumor types.

The majority of the cancers in the cohort F of the GARNET study were gastrointestinal, such as colorectal, gastric and small intestinal cancers. Cohort A1 looked at dMMR/MSI-H endometrial cancer, cohort A2 looked at mismatch repair proficient/microsatellite stable (MMRp/MSS) endometrial cancer, cohort E is evaluating non-small cell lung cancer, cohort F is studying dMMR/MSI-H non-endometrial cancer or POLE-mut solid tumor basket, and cohort G is studying platinum-resistant ovarian cancer without BRCA mutations.