FDA Grants Accelerated Approval to Dostarlimab-Gxly for dMMR Endometrial Cancer
On April 22, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-endometrial-cancer) to dostarlimab-gxly (Jemperli), an anti-PD-1 antibody, 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 treatment with a prior platinum-containing regimen.
FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device for selecting patients with endometrial cancer for treatment with dostarlimab-gxly.
Efficacy was evaluated based on cohort A1 in a multicenter, multicohort, open-label trial (GARNET; NCT02715284) of patients with advanced solid tumors, which consisted of 71 patients with dMMR recurrent or advanced endometrial cancer who progressed on or after a platinum-containing regimen. Patients received dostarlimab-gxly 500 mg via IV infusion every three weeks for four doses followed by 1,000 mg via IV infusion every six weeks.
The main efficacy endpoints were overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review according to response evaluation criteria in solid tumors 1.1. The confirmed ORR was 42.3% (95% CI = 30.6%, 54.6%), complete response rate was 12.7%, and partial response rate was 29.6%. Median DOR was not reached, but researchers reported that 93.3% of patients responded for at least six months (range = 2.6–22.4 months, ongoing at last assessment).
Serious adverse reactions occurred in 34% of patients receiving dostarlimab-gxly. Those that occurred in more than 2% of patients were sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia. The most common any-grade adverse reactions (≥ 20%) were fatigue, asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (≥ 2%) were anemia and increased transaminases. Immune-mediated adverse reactions can occur, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
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.
FDA granted accelerated approval to the indication based on tumor response rate and durability of response. Continued approval is contingent on verification and description of clinical benefit in confirmatory trials.
The review used the Real Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program) pilot program, which streamlined data submission prior to filing the entire clinical application, and Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application priority review and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or 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 oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).