Dostarlimab, Diagnostic Cleared for Advanced Endometrial Cancer With Specific Biomarker

This month, the FDA granted accelerated approval for dostarlimab for patients with recurrent or advanced deficient mismatch repair (dMMR) endometrial cancer (EC) that has advanced on or after platinum-containing chemotherapy. At the same time, the FDA approved the VENTANA MMR RxDx Panel, an immunohistochemistry companion diagnostic for dostarlimab.

Dostarlimab, to be marketed as Jemperli by GlaxoSmithKline, is a PD-1 inhibitor and is the first immunotherapy advance in EC, which has limited treatment options if first-line therapy fails. EC has increasing incidence and mortality, and about 25% to 30% of patients with advanced endometrial cancer have dMMR tumors.

It previously received Breakthrough Therapy designation from the FDA in May 2019.

The data supporting the decision for the PD-1 inhibitor come from a single-arm, multi-cohort, non-randomized, open-label GARNET trial (NCT02715284). Of the 71 patients with dMMR recurrent or advanced EC on dostarlimab in the trial, 42.3% had a complete response or a partial response. For 93% of responders, the response lasted for 6 months or more.

Patients received 500 mg of dostarlimab once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression.

The safety population included all patients with dMMR disease who had received dostarlimab (n = 104). Only 2% of patients discontinued the drug because of treatment-related adverse events (TRAEs), which is consistent with the safety profiles of other approved PD-1 inhibitors. The most common TRAEs were asthenia (15%), diarrhea (15%), fatigue (14%), and nausea (13%). There were no grade 5 events reported.

“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,” said

Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, in a statement.

The therapy also received Priority Review, and full approval depends on further clinical trials to verify and describe its clinical benefit in this setting.

The VENTANA MMR RxDx Panel is marketed by Roche and is a label expansion of the company’s currently available VENTANA MMR IHC Panel. VENTANA MMR RxDx is a qualitative IHC test designed for use in assessing the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. The proteins are assessed in formalin-fixed, paraffin-embedded endometrial carcinoma tissue through light microscopy.