Dostarlimab Gains New FDA-Approved Indication for Treatment of Mismatch Repair–Deficient Tumors

The FDA has approved a new indication for dostarlimab (Jemperli) as therapy for patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors that have progressed on or after prior therapy and have no suitable treatment alternatives, according to the agent’s manufacturer GlaxoSmithKline.

The decision is supported by data from the phase 1 single-arm, multi-cohort GARNET trial (NCT02715284), which included 209 patients with dMMR advanced solid tumors who were treated with the anti–PD-1 monoclonal antibody.

This indication follows an accelerated approval for dostarlimab as therapy for patients with recurrent or advanced deficient mismatch repair (dMMR) endometrial cancer that has progressed on or following prior treatment with platinum-containing chemotherapy, as determined by an FDA-approved test for which data from the GARNET trial served to support the indication.

“Dostarlimab is an important new treatment option for patients with mismatch repair-deficient recurrent or advanced solid cancers who have progressed and have no alternative options,” Jubilee Brown, MD, professor and Division Director of Gynecologic Oncology at Atrium Health, Levine Cancer Institute, said in a press release. “As we saw in the GARNET trial, of those patients who respond to treatment with dostarlimab, nearly all continued to respond for six months or longer.”

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

Of all patients in the dMMR population, 41.6% (95% CI, 34.9%-48.6%) had an objective response (ORR) to therapy, comprised of 9.1% complete responses and 32.5% partial responses. In 106 patients with non-endometrial tumors, the ORR was 38.7% (95% CI, 29.4%-48.6%).

In the overall population, the median duration of response was 34.7 months (range, 2.6-35.8+) and the rate of maintained response at 6 months was 95.4%.

The most common all-grade adverse effects of dostarlimab included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). Grade 3 or 4 AEs and laboratory abnormalities that occurred in 2% of patients or more included anemia, fatigue/asthenia, increased transaminases, sepsis, acute kidney injury, decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin.

Reference

GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours. GlaxoSmithKline. News release. August 17, 2021. Accessed August 17, 2021. https://bit.ly/3iQxHnj