Dostarlimab-gxly Approved For dMMR Endometrial Cancer

Endometrial cancer cells.

The FDA has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline LLC) for treatment of mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen or who are not eligible for curative surgery or radiation. Diagnosis is determined by an FDA-approved test.

“Endometrial cancer is the most common gynecologic malignancy in the developed world and has the highest rate of dMMR/microsatellite instability–high (MSI-H) status of any tumor type; up to 30% of all endometrial cancers are classified as dMMR/MSI-H,” wrote Ana Oaknin, MD, Head of the Gynaecological Tumour Unit at the Intitute of Oncology, Hospital Quirónsalud Barcelona, and colleagues in their published results of the GARNET trial (NCT02715284), on which approval was based. “Dostarlimab is a humanized monoclonal antibody that binds with high affinity to programmed cell death protein 1 (PD-1), resulting in inhibition of binding to programmed death ligand 1 (PD-L1) and PD-L2.”

Safety and efficacy were determined in the phase 1 open-label, single-arm, multicenter trial in which a cohort of 141 patients with dMMR recurrent or advanced endometrial cancer were given 500 mg of dostarlimab every three weeks for four cycles, then 1,000 mg of dostarlimab every six weeks until disease progression. Each dose was given via intravenous infusion over 30 minutes. Eligible patients had progressed on or after a platinum-containing regimen; patients who had received previous PD-1/PD-L1–blocking antibodies, other immune checkpoint inhibitors, or systemic immunosuppressant agents for autoimmune diseases were excluded.

The primary end points measured were overall response rate and duration of response as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The confirmed overall response rate was 45.4%, including 15.6% of patients achieving a complete response and 29.8% achieving a partial response. The overall median duration of response was not reached, with 85.9% achieving a response for ≥12 months and 54.7% achieving a response for ≥24 months.

The most common adverse events in ≥20% of patients were fatigue, 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.

“Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H and mismatch repair–proficient/microsatellite-stable (MMRp/MSS) endometrial cancer with a manageable safety profile,” concluded Dr. Oaknin and colleagues. “Consistent with previous reports, confirmed dMMR status by immunohistochemistry or MSI status by polymerase chain reaction or next-generation sequencing was associated with a higher response rate.”

The recommended dosage is 500 mg of dostarlimab-gxly, scheduled every three weeks for doses one through four. Starting three weeks after dose four, the recommended dosage is 1,000 mg every six weeks until disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered as an intravenous infusion over 30 minutes.

For More Information

Oaknin A, Gilbert L, Tinker A, et al (2022). Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET—a phase I, single-arm study. J Immunother Cancer, 10(1):e003777. DOI:10.1136/jitc-2021-003777

Clinicaltrials.gov (2022). Study of TSR-042, an anti-programmed cell death-1 receptor (PD-1) monoclonal antibody, in participants with advanced solid tumors (GARNET). NLM identifier: NCT02715284.

Jemperli (dostarlimab-gxly) prescribing information (2023). GlaxoSmithKline. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761174s003s004lbl.pdf

US Food and Drug Administration (2023). FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer 

Image credit: Mikael Häggström. Licensed under CC0 1.0


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