FDA Grants Regular Approval to Dostarlimab-Gxly for dMMR Endometrial Cancer
On February 9, 2023, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer) dostarlimab-gxly (Jemperli®) for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.
In April 2021, dostarlimab-gxly received accelerated approval (https://voice.ons.org/news-and-views/fda-grants-accelerated-approval-to-dostarlimab-gxly-for-dmmr-endometrial-cancer) for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen.
Efficacy for the regular approval was evaluated in GARNET (NCT02715284), a multicenter, multicohort, open-label trial conducted in patients with advanced solid tumors. The efficacy population consisted of 141 patients with dMMR recurrent or advanced endometrial cancer who had progressed on or after a platinum-containing regimen. Patients were excluded if they had been treated with prior PD-1/PD-LI-blocking antibodies or other immune checkpoint inhibitors or had autoimmune diseases requiring systemic immunosuppressant agents within two years.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review according to RECIST v1.1. Confirmed ORR was 45.4% (95% CI = 37.0, 54.0), with a 15.6% complete response rate and a 29.8% partial response rate. Median DOR was not reached, with 85.9% of patients having durations for at least 12 months and 54.7% of patients having durations for at least 24 months (range = 1.2+, 52.8+).
The most common adverse reactions that occurred in at least 20% of patients treated with dostarlimab-gxly were fatigue or asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. Immune-mediated adverse reactions can occur, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.
The recommended dostarlimab-gxly dose and schedule (doses 1–4) is 500 mg every three weeks. Subsequent dosing, beginning three weeks after the fourth dose, is 1,000 mg every six weeks until patients experience disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered via IV infusion over 30 minutes.
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate the FDA’s assessment. FDA approved the application one month ahead of the FDA goal date.
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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications for oncology products, healthcare professionals may contact OCE’s Project Facilitate (mailto:OCE%E2%80%99s%20Project%20Facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).