FDA Approves Dostarlimab-gxly for Endometrial Cancer With dMMR or MSI-H Mutation

On July 31, 2023, the U.S. Food and Drug Administration approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) for primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). Mismatch repair deficiency must be determined by an FDA-approved test. 

 

Study ID number: NCT03981796

 

Approval was based on the RUBY trial, a randomized, multicenter international, double-blind trial that evaluated the efficacy of dostarlimab-gxly in a pre-specified subgroup of 122 patients. The patients were randomized (1:1) to either carboplatin and paclitaxel with dostarlimab-gxly followed by single-agent dostarlimab-gxly or carboplatin and paclitaxel with placebo, followed by placebo alone. The recommended dosing for dostarlimab-gxly was 500 mg every three weeks for six doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every six weeks until disease progression or unacceptable toxicity or up to 3 years. Dostarlimab-gxly was administered before chemotherapy when given on the same day.

 

Efficacy was determined by investigator-assessed progression-free survival (PFS). The study demonstrated a statistically significant improvement in (PFS) in patients with dMMR/MSI-H population, with a median PFS of 30.3 months for the dostarlimab-gxly subgroup versus 7.7 months in the placebo subgroup (Hazard Ratio=0.29 [95% CI: 0.17, 0.50]; p-value<0.0001).

 

Side effects of dostarlimab-gxly included immune-mediated adverse reactions, such as pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism), renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥20%) observed with dostarlimab-gxly in combination with carboplatin and paclitaxel were rash, diarrhea, hypothyroidism, and hypertension.

 

Dostarlimab-gxly (Jemperli) has been approved for the treatment of primary advanced or recurrent endometrial cancer (EC) with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) mutation. The approval was based on the results of the RUBY trial (NCT03981796), which showed a significant improvement in progression-free survival (PFS) for patients receiving dostarlimab-gxly compared to the placebo. The medication is associated with immune-mediated adverse reactions, and the recommended dosing regimen includes a combination of carboplatin and paclitaxel followed by monotherapy. Healthcare professionals should refer to the prescribing information for complete details and individualized treatment decisions.