FDA Approves Dostarlimab-Gxly for Mismatch Repair Deficient Advanced Solid Tumors

Solid tumor.

The FDA has granted accelerated approval to dostarlimab-gxly (Jemperli, GlaxoSmithKline) for patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors that have progressed on or following prior treatment and have no other satisfactory alternative options. In addition, the FDA approved the VENTANA MMR RxDx Panel as a companion diagnostic to determine eligibility for treatment with dostarlimab.

“Dostarlimab is an investigational, humanized programmed cell death protein 1 (PD-1) receptor monoclonal antibody that blocks interactions with the PD-1 ligands, programmed cell death ligand-1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2),” wrote Dominique Berton, MD, an oncologist at the ICO Centre René-Gauducheau in France, and colleagues, in their abstract of the results of the GARNET study (NCT02715284), on which the approval was based.

This non-randomized, multicenter, open-label, multicohort, single-arm trial enrolled 209 patients with dMMR recurrent or advanced solid tumors who were not eligible for any satisfactory alternative treatment. Patients received 500 mg of dostarlimab administered intravenously every three weeks for four cycles, followed by 1,000 mg of dostarlimab administered intravenously every six weeks until disease progression or discontinuation. The primary end points were overall response rate and duration of response.

At a minimum follow-up of six months, dostarlimab produced an overall response rate of 41.6%, with a complete response rate of 9.1%. The median duration of response was 34.7 months, with 95.4% of patients experiencing a response lasting at least 6 months.

Adverse events occurring in at least 20% of patients included fatigue/asthenia, anemia, diarrhea, and nausea. Grade 3 or 4 adverse events occurring in at least 2% of patients included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Immune-mediated adverse events include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic toxicity.

“Dostarlimab demonstrated durable antitumor activity in patients with dMMR solid tumors, with consistent antitumor activity seen across endometrial and nonendometrial tumor types,” concluded Dr. Berton and colleagues in their May 2021 abstract, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology. “Most treatment-related adverse events were low grade and were similar across cohorts.”

The recommended dose of dostarlimab is 500 mg every three weeks for Doses 1-4, administered as an intravenous infusion over 30 minutes. Beginning three weeks after Dose 4, subsequent dosing is 1,000 mg every six weeks.

For More Information

Berton D, Banerjee SN, Curigliano G, et al (2021). Antitumor activity of dostarlimab in patients with mismatch repair-deficient/microsatellite instability-high tumors: a combined analysis of two cohorts in the GARNET study. J Clin Oncol (ASCO Annual Meeting Abstracts), 39(suppl_15). Abstract 2564. DOI:10.1200/JCO.2021.39.15_suppl.2564

Clinicaltrials.gov (2021). Study of TSR-042, an anti-programmed cell death-1 (PD-1) monoclonal antibody, in participants with advanced solid tumors (GARNET). NLM identifier: NCT02715284.

Jemperli (dostarlimab-gxly) prescribing information (2021). GlaxoSmithKline. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761223s000lbl.pdf

US Food & Drug Administration. FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors

Image credit: Nephron. Licensed under CC BY-SA 3.0

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