On July 31, 2023, the immune checkpoint inhibitor dostarlimab-gxly was approved by the U.S. Food and Drug Administration (FDA) for use with carboplatin and paclitaxel, followed by single-agent dostarlimab, for patients with primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability–high (MSI-H).¹

Supporting Efficacy Data

Approval was based on findings in a prespecified subgroup of 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in the double-blind RUBY trial (ClinicalTrials.gov identifier NCT03981796). Patients were randomly assigned to receive dostarlimab (n = 60) or placebo (n = 62) with carboplatin and paclitaxel followed by dostarlimab or placebo.

Investigator-assessed median progression-free survival was 30.3 months (95% confidence interval [CI] = 11.8 months to not reached) in the dostarlimab group vs 7.7 months (95% CI = 5.6–9.7 months) in the placebo group (hazard ratio = 0.29, 95% CI = 0.17–0.50, P < .0001).

How It Is Used

The recommended dostarlimab dose is 500 mg every 3 weeks for six doses with carboplatin and paclitaxel, followed by 1,000 mg of monotherapy every 6 weeks until disease progression or unacceptable toxicity or up to 3 years. Dostarlimab should be administered before chemotherapy when given on the same day. No dose reductions for dostarlimab are recommended. Product labeling provides instructions on dosage modification for immune-mediated adverse reactions and infusion-related reactions.

Safety Profile

The most common adverse events of any grade with dostarlimab in combination with carboplatin and paclitaxel were rash (42% vs 20% with placebo plus chemotherapy), diarrhea (40% vs 31%), hypothyroidism (23% vs 6%), and hypertension (21% vs 11%). The most common grade 3 or 4 adverse events in the dostarlimab group included hypertension (10% vs 6%) and rash (6% vs 0%). The most common grade 3 or 4 laboratory abnormalities in the dostarlimab group were decreased neutrophils (21%), decreased hemoglobin (17%), decreased lymphocytes (13%), increased glucose (13%), and decreased sodium (12%).

Serious adverse events occurred in 13% of patients in the dostarlimab group, most commonly sepsis, including urosepsis (6%). Adverse events led to discontinuation of dostarlimab in 15% of patients. Fatal adverse events occurred in 6% of patients in the dostarlimab group, including septic shock.

Dostarlimab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving dostarlimab. 

REFERENCE

1. Jemperli (dostarlimab-gxly) injection, for intravenous use, prescribing information, GlaxoSmithKline, July 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761174s006lbl.pdf. Accessed August 10, 2023.