On August 17, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to dostarlimab-gxly (Jemperli®) for adult patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

FDA Grants Accelerated Approval to Dostarlimab-gxly for dMMR Advanced Solid Tumors

FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device to identify patients with dMMR solid tumors who are appropriate for treatment with dostarlimab-gxly.

Efficacy of dostarlimab-gxly was evaluated in a nonrandomized, multicenter, open-label, multicohort trial (GARNET, NCT02715284). The efficacy population consisted of 209 patients with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment options. The primary efficacy endpoints were overall response rate (ORR) and duration of response (DoR), as determined by blinded independent central review according to the response evaluation criteria in solid tumors 1.1. The ORR was 41.6% (95% CI = 34.9, 48.6), with 9.1% complete response rate and 32.5% partial response rate. Median DoR was 34.7 months (range = 2.6–35.8+), and overall DoR was at least 6 months for 95.4% of patients.

Most common (≥ 20%) adverse reactions reported in patients with dMMR solid tumors are fatigue or asthenia, anemia, diarrhea, and nausea. Most common (≥ 2%) grade 3 or 4 adverse reactions reported were anemia, fatigue or asthenia, increased transaminases, sepsis, and acute kidney injury. Immune-mediated adverse reactions were also associated with dostarlimab-gxly, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic toxicity.

The recommended dostarlimab-gxly dosage is 500 mg every three weeks for dose 1–4, administered via IV infusion over 30 minutes. Subsequent dosing beginning three weeks after dose 4 is 1,000 mg every six weeks.

View the full prescribing information for dostarlimab-gxly.

The indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for the indication may be contingent on verification and description of clinical benefit in confirmatory trials.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.