FDA Grants Tissue-Agnostic Approval to Dostarlimab for dMMR Tumors

— Overall response rate of 41.6% in various tumor types with mismatch repair deficiency

by Charles Bankhead, Senior Editor, 番茄社区 August 18, 2021

FDA APPROVED over a computer rendering of a tumor.

The FDA granted a fifth tissue-agnostic indication, expanding approved use of the PD-1 inhibitor dostarlimab (Jemperli) for any solid tumor with .

Dostarlimab's initial approval was limited to uterine/endometrial cancer associated with dMMR. The new indication removes limitations on tumor type, a potentially substantial increase in the indicated patient population. The other drugs with are the PD-1 inhibitor pembrolizumab (Keytruda) for solid tumors with dMMR/microsatellite instability (MSI)-high status or high tumor mutational burden; and the NTRK inhibitors entrectinib (Rozlytrek) and larotrectinib (Vitrakvi).

Support for the accelerated approval for dMMR tumors came from the phase I study, which showed an overall response rate of 41.6% in 209 patients with dMMR malignancies, including endometrial and non-endometrial cancers. Median duration of response was 34.7 months, and responses lasted 6 months or longer in 95.4% of cases. In the 106-patient cohort with non-endometrial cancers, dostarlimab led to an ORR of 38.7%

"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," said Jubilee Brown, MD, of the Atrium Health Levine Cancer Institute in Charlotte, North Carolina, in a statement from GlaxoSmithKline. "As we saw in the GARNET trial, of those patients who respond to treatment with dostarlimab, nearly all continued to respond for 6 months or longer."

In the GARNET trial, adverse events (AEs) occurring in at least 20% of patients consisted of fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3/4 AEs were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Grade 3/4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin.

Full approval of the tissue-agnostic indication remains contingent on accumulation of supportive data from additional studies.

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined 番茄社区 in 2007.