On August 17, 2021, the FDA accelerated the approval of dostarlimab-gxly (Jemperli; GlaxoSmithKline) for adults with mismatch repair-deficient (dMMR), as determined by an FDA-approved test, recurrent or advanced solid tumors that progressed during or after treatment for whom there are no satisfactory alternative options.
On the same day, the FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic test to select appropriate candidates for dostarlimab therapy. Dostarlimab was initially approved in April 2021 for endometrial cancer.
The FDA approval of dostarlimab for this indication was based on the GARNET study, a nonrandomized, multicenter, open-label, multicohort clinical trial of 209 patients with dMMR recurrent or advanced solid tumors that progressed after systemic therapy.
The primary end points were overall response rate (ORR) and duration of response (DOR). The ORR was 41.6%, including 9.1% complete responses and 32.5% partial responses. The median DOR was 34.7 months; 95.4% of the patients had a response lasting ≥6 months.
The most common (≥2%) grade 3 or 4 adverse events were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Immune-mediated adverse reactions associated with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic toxicity.