FDA Grants Tissue-Agnostic Approval to Dostarlimab for dMMR Tumors

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

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 FDA-approved tissue-agnostic indications 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 GARNET 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.