The Food and Drug Administration (FDA) has granted accelerated approval to Jemperli (dostarlimab-gxly) for the treatment of adults with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen.
Dostarlimab is a programmed death receptor-1 (PD-1) blocking antibody that works by targeting the PD-1/PD-L1 cellular pathway resulting in the inhibition of T-cell proliferation and cytokine production. The accelerated approval was based on data from the multicenter, multicohort, open-label phase 1 GARNET trial (ClinicalTrials.gov: NCT02715284) that evaluated dostarlimab in 71 adults with dMMR recurrent or advanced endometrial cancer who progressed on or after a platinum-containing regimen.
Patients received dostarlimab 500mg intravenously (IV) every 3 weeks for 4 doses followed by 1000mg IV every 6 weeks until disease progression or unacceptable toxicity. The major efficacy endpoints were overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR) according to RECIST v1.1.
Findings showed an ORR of 42.3% (95% CI, 30.6-54.6), with 12.7% of patients achieving complete response and 29.6% having partial response. The median DOR was not reached with 93.3% of patients having a response lasting at least 6 months (range: 2.6-22.4+).
As for safety, the most common adverse reactions (³20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (³2%) were anemia and increased transaminases. Serious adverse reactions that occurred in greater than 2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia.
“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population.”
The VENTANA MMR RxDx Panel was also approved as a companion diagnostic device for selecting endometrial cancer patients for treatment with Jemperli.
Jemperli is supplied in 10mL single-dose vials, each containing 500mg of dostarlimab-gxly.
- FDA grants accelerated approval to dostarlimab-gxly for dMMR endometrial cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; April 22, 2021.
- FDA approves immunotherapy for endometrial cancer with specific biomarker. [press release]. Silver Spring, MD: US Food and Drug Administration; April 22, 2021.
- Jemperli [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021.