FDA approves Jemperli for mismatch repair-deficient solid tumors
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The FDA granted accelerated approval to dostarlimab-gxly for adults with mismatch repair-deficient recurrent or advanced solid tumors that progressed on or after prior treatment and who have no satisfactory alternative therapies.
The agency also approved the Ventana MMR RxDx Panel (Roche), a companion diagnostic test designed to help identify patients with mismatch repair-deficient solid tumors who may be eligible for dostarlimab-gxly (Jemperli, GlaxoSmithKline).
An estimated 14% of solid tumors diagnosed in the United States are mismatch repair deficient. This biomarker — most often found in endometrial, colorectal and other gastrointestinal cancers — has been shown to predict response to immune checkpoint blockade with PD-1 therapy.
Dostarlimab-gxly — a PD-1-blocking antibody — previously received approval in the United States for women with mismatch repair-deficient recurrent or advanced endometrial cancer that progressed on or after a platinum-containing regimen.
The FDA based the new indication on results from two cohorts of the phase 1 GARNET study, designed to evaluate dostarlimab-gxly as monotherapy for patients with advanced, mismatch repair-deficient solid tumors. One cohort included patients with endometrial cancer. The other included patients with non-endometrial cancers, the most common of which were colorectal, small intestine and stomach cancers.
Patients received 500 mg dostarlimab-gxly via IV infusion every 3 weeks for four doses, followed by 1,000 mg once every 6 weeks. Treatment continued until disease progression or unacceptable toxicity.
Objective response rate and duration of response served as major efficacy outcomes.
Results of the multicenter, nonrandomized study showed a 41.6% ORR among all patients with mismatch repair-deficient solid tumors, with a 9.1% complete response rate and 32.5% partial response rate. Nearly all responses (95.4%) lasted at least 6 months. Median duration of response was 34.7 months (range, 2.6-35.8+).
A safety analysis included 267 evaluable patients. The most commonly reported adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%) and nausea (22%). The most common grade 3 or grade 4 adverse events included anemia, fatigue/asthenia, increased transaminases, sepsis and acute kidney injury. Grade 3 or grade 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased alkaline phosphatase and decreased albumin.
Verification and description of clinical benefit in a confirmatory trial may be necessary to ensure continued approval for this indication, according to a GlaxoSmithKline-issued press release.
“For patients with tumors expressing the [mismatch repair-deficient] biomarker, there continues to be a significant need for new and effective treatments. I’m excited about GSK’s second oncology FDA approval this year, and the new treatment option it provides for these patients,” Hal Barron, MD, chief scientific officer and president of research and development for GlaxoSmithKline, said in the release.
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