FDA Approves Dostarlimab for dMMR Recurrent/Advanced Endometrial Cancer

The FDA has granted approval to dostarlimab (Jemperli) for the treatment of patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.¹

Approval of dostarlimab for this indication is supported by findings from the phase 1 multicenter, multicohort, open-label GARNET trial (NCT02715284). Results from a third interim analysis of the study were published in the Journal of Clinical Oncology in 2022.²

The GARNET study is a multicenter, open-label, single-arm phase 1 study. In cohort A1, patients were enrolled if they had dMMR/MSI-H endometrial cancer. The other cohort of patients were those with dMMR/MSI-H/POLε-mutant non-endometrial cancer solid tumors.

The overall goal of the study was to evaluate the efficacy of dostarlimab monotherapy in patients with advanced or recurrent solid tumors. In 153 patients with dMMR/MSI-H endometrial cancer, 210 with dMMR/MSI-H and POLε-mutated solid tumors other than endometrial. Patients were given 500 mg dostarlimab intravenously (IV) every 3 weeks for 4 cycles, followed by 1000 mg dostarlimab IV every 6 weeks until disease progression, discontinuation, or withdrawal.

At a median follow-up of 27.6 months in the endometrial cancer cohort and 27.7 months in the solid tumor cohort, the objective response rate (ORR) was 45.5% (95% CI, 37.1%-54.0%) and 43.1% (95% CI, 36.2%-50.2%), respectively. The median duration of response was not reached in either arm, and responses were ongoing at data cutoff in 83.1% of the endometrial cancer population and 87.5% of the solid tumor group.

The median progression-free survival (mPFS) was 6.0 months (95% CI, 4.1-18.0 months) in the endometrial cancer cohort and 7.1 months (95% CI, 3.6-19.5 months) in the solid tumor cohort. The mOS was not reached in either arm.

Regarding safety, treatment-emergent adverse events (TRAEs) that occurred in 12% of patients or more included diarrhea, asthenia, fatigue, nausea, and pruritis in the patients with dMMR/MSI-H endometrial cancer and diarrhea, asthenia, and pruritus in patients with dMMR/MSI-H/POLε-mut non-endometrial cancer arm. In patients with non-endometrial cancer, there were 2 deaths, including 1 as a result of hepatic ischemia and 1 due to suicide.

Overall, dostarlimab elicited durable antitumor activity across 16 tumor types in patients with dMMR solid tumors. Data from GARNET proves the efficacy in this patient population with an extended follow-up. Additionally, the safety profile was acceptable and there were manageable toxicities.

_REFERENCES:

_{1. FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. News release. FDA. February 9, 2023. Accessed February 9, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer}

_{2. Thierry A, Berton D, Curigliano G, et al. Efficacy and safety of dostarlimab in patients (pts) with mismatch repair deficient (dMMR) solid tumors: Analysis of 2 cohorts in the GARNET study. J Clin Oncol. 2022;40(16):2587-2587. doi:10.1200/JCO.2022.40.16_suppl.2587}