Conversion from accelerated to regular approval was based on long-term outcomes from a phase 1 trial, which demonstrated an overall response rate of 45.4%.
The FDA has converted the accelerated approval of GSK’s Jemperli (dostarlimab-gxly) to a full approval to treat patients with advanced endometrial cancer. It is indicated for patients who have a mismatch repair-deficient (dMMR) cancer that has progressed following a prior treatment. In April 2021, Jemperli received accelerated approval for this indication.
Endometrial cancer is the most common gynecologic cancer globally, with about 417,000 new cases reported each year worldwide. About 15% to 20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.
The price of Jemperli is about $11,540 per 500 mg/10 mL vial, which is initially given once every three weeks for four doses, according to Drugs.com. GSK offers co-pay assistance of up of $26,000 for patients with commercial insurance.
The full approval is based on additional data collected from the A1 expansion cohort of the ongoing GARNET trial, a phase I single-arm study of Jemperli monotherapy in patients with advanced or recurrent solid tumors. Cohort A1 evaluated the efficacy of Jemperli in 141 patients with dMMR advanced or recurrent endometrial cancer. Confirmed overall response rate (ORR) was 45.4%, with a 15.6% complete response rate and a 29.8% partial response rate.
Treatment-related adverse events were consistent with previous analyses for cohort A1. The most common adverse reactions were fatigue/asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. The most common grade 3 or 4 adverse reactions were anemia, increased transaminases, urinary tract infection, fatigue/asthenia, and diarrhea.
The full approval for the endometrial cancer indication comes just one day after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted to support a phase 2 trial of Jemperli in patients with advanced rectal cancer. The regulatory agency recently granted fast track designation to Jemperli in rectal cancer patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H). The trial will study Jemperli as monotherapy for treatment-naïve patients with this cancer. The primary endpoint of GSK’s proposed trial is clinical complete response for 12 months.
The FDA held an advisory committee meeting because of concerns about the single-arm, open label study using tumor complete response as an endpoint and whether that could support accelerated approval. In voting yes to support the trial, some committee members mentioned that a randomized trial might be difficult because of the small number of patients with this disease and the biomarker and the data should be sufficient. About 5% to 10% of all rectal cancers are dMMR/MSI-H.
Committee members, however, mentioned that interpreting the data could be challenging because of variability in the biomarker.