The Food and Drug Administration (FDA) has granted accelerated approval to Jemperli (dostarlimab-gxly) for the treatment of 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.
Dostarlimab-gxly 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 Identifier: NCT02715284) that evaluated dostarlimab in 209 adults with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment options.
Patients received dostarlimab-gxly 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 according to RECIST v1.1.
Among all patients with dMMR solid tumors including endometrial and non-endometrial, results showed an ORR of 41.6% (95% CI, 34.9 to 48.6), with 9.1% achieving complete response and 32.5% having partial response. The median DOR was 34.7 months with 95.4% of patients having a response lasting at least 6 months (range, 2.6 to 35.8+). In the dMMR solid tumor non-endometrial cancer cohort (n=106), results showed an ORR of 38.7% (95% CI, 29.4 to 48.6).
As for safety, the most common adverse reactions reported were fatigue/asthenia, anemia, diarrhea, and nausea. The most common grade 3 or 4 adverse reactions were anemia, fatigue/asthenia, increased transaminases, sepsis and acute kidney injury.
In April 2021, the FDA also granted accelerated approval to Jemperli for the treatment of adults with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that have progressed on or following prior treatment with a platinum-containing regimen.
The approval was based on cohort A1 from the GARNET trial, which included 71 patients with dMMR endometrial cancer. Updated findings from an additional 32 patients with dMMR endometrial cancer (n=103) showed an ORR of 44.7% (95% CI, 34.9 to 54.8) with a DOR range of 2.6-35.8+ months.
The VENTANA MMR RxDx Panel was also approved as a companion diagnostic device for selecting patients with dMMR solid tumors for treatment with Jemperli.
Jemperli is supplied as 10mL single-dose vials, each containing 500mg of dostarlimab-gxly.
- GSK receives FDA accelerated approval for Jemperli (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors. News release. GlaxoSmithKline. Accessed August 18, 2021. https://www.prnewswire.com/news-releases/gsk-receives-fda-accelerated-approval-for-jemperli-dostarlimab-gxly-for-adult-patients-with-mismatch-repair-deficient-dmmr-recurrent-or-advanced-solid-tumors-301357348.html.
- FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. News release. US Food and Drug Administration. Accessed August 18, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors?utm_medium=email&utm_source=govdelivery.
- FDA grants accelerated approval of Jemperli (dostarlimab-gxly) for dMMR recurrent or advanced solid tumors. News release. AnaptysBio, Inc. Accessed August 18, 2021. https://www.globenewswire.com/news-release/2021/08/17/2282311/0/en/FDA-Grants-Accelerated-Approval-of-JEMPERLI-dostarlimab-gxly-for-dMMR-Recurrent-or-Advanced-Solid-Tumors.html.
- Jemperli [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021.