On August 17, 2021, dostarlimab-gxly, aPD-1 blocking monoclonal antibody, was granted accelerated approval for adults with mismatch repair–deficient (dMMR) recurrent or advanced solid tumors, as determined by a U.S. Food and Drug Administration (FDA)-approved test, who have had disease progression after prior systemic therapy and have no satisfactory alternative treatment options.1 The Ventana MMR RxDx Panel was simultaneously approved as a companion diagnostic device to select patients with dMMR solid tumors for dostarlimab treatment.
Supporting Efficacy Data
Approval was based on findings in the multicenter, multicohort GARNET trial (ClinicalTrials.gov identifier NCT02811861).1 In this study, an efficacy population of 209 patients received dostarlimab at 500 mg intravenously (IV) every 3 weeks for four doses, followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity.
On blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1, the objective response rate was 41.6% (95% confidence interval [CI] = 34.9%–48.6%), with a complete response in 9.1%. The median duration of response was 34.7 months (range 2.6 = 35.8+ months), with 95.4% of responders having a response of at least 6 months.
How It Is Used
Patients must be selected for treatment based on the presence of dMMR in tumor specimens, as determined by an FDA-approved test. The recommended dosage is 500 mg via 30-minute IV infusion every 3 weeks for doses 1 through 4, followed at 3 weeks after dose 4 with 1,000 mg every 6 weeks.
KEY POINTS
- Dostarlimab-gxly was granted accelerated approval for adults with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, who have had disease progression after prior systemic therapy and have no satisfactory alternative treatment options.
- The recommended dosage is 500 mg via 30-minute IV infusion every 3 weeks for doses 1 through 4, followed at 3 weeks after dose 4 with 1,000 mg every 6 weeks.
No dose reductions for dostarlimab are recommended. In general, dostarlimab should be withheld for grade 3 immune-mediated adverse reactions and permanently discontinued for grade 4 immune-mediated adverse reactions, recurrent grade 3 immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce the corticosteroid dose to ≤ 10 mg/d of prednisone or the equivalent within 12 weeks of initiating steroids.
Safety Profile
Among 267 patients receiving dostarlimab at the recommended dose in the GARNET trial, the most common any-grade adverse events (≥ 20%) were fatigue/asthenia, anemia, diarrhea, and nausea. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes and increased sodium.
Serious adverse events occurred in 34% of patients, most commonly abdominal pain, sepsis, and acute kidney injury. Adverse events led to discontinuation of treatment in 9%. Adverse events led to death in one patient, due to respiratory failure.
REFERENCE
1. Jemperli (dostarlimab-gxly) injection, for intravenous use, prescribing information, GlaxoSmithKline LLC, August 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761223s000lbl.pdf. Accessed August 26, 2021.
