Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the US as a monotherapy in pts with dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; or dMMR advanced/recurrent (AR) endometrial cancer (EC) that has progressed on or after treatment with a platinum-based chemo; and in the EU as a monotherapy in pts with dMMR/microsatellite instability?high (MSI-H) AR EC that has progressed on or after treatment with a platinum-based chemo. Here we report on efficacy and safety in 2 expansion cohorts that enrolled pts with dMMR solid tumors. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Cohort A1 enrolled pts with dMMR/MSI-H AR EC; cohort F enrolled pts with dMMR/MSI-H/POLε-mut non-EC solid tumors. Pts received 500 mg of IV dostarlimab Q3W for 4 cycles, then 1000 mg Q6W until PD, discontinuation, or withdrawal. Primary endpoints were ORR and DOR by BICR per RECIST v1.1. Biomarker status was based on local assessment. Results: For this third interim analysis, 153 pts with dMMR/MSI-H EC and 210 pts with dMMR/MSI-H/POLε-mut non-EC solid tumors (56% colorectal cancer, 11% gastric) were enrolled and treated. Efficacy analysis was performed for 143 dMMR/MSI-H EC and 204 dMMR/MSI-H/POLε-mut non-EC pts who had measurable disease at baseline and ≥6 mo of follow-up. ORRs were 45.5% (dMMR/MSI-H EC) and 43.1% (dMMR/POLε-mut non-EC solid tumors; Table). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 51.8%, 48.1%, and 46.4% in dMMR/MSI-H/POLε-mut non-EC. Median (m) DOR and mOS were not reached for either cohort. A total of 13 pts (8.5%) with dMMR/MSI-H EC and 12 pts (5.7%) with dMMR/MSI-H/POLε-mut non-EC solid tumors discontinued owing to a treatment-related adverse event (TRAE). TRAEs occurring in ≥12% of pts were diarrhea, asthenia, fatigue, nausea, and pruritis (dMMR/MSI-H EC) and diarrhea, asthenia, and pruritus (dMMR/MSI-H/POLε-mut non-EC solid tumors). 2 deaths (1 hepatic ischemia, 1 suicide) were attributed by investigators to dostarlimab in pts with non-EC solid tumors. Conclusions: Dostarlimab demonstrated durable antitumor activity across 16 tumor types in pts with dMMR solid tumors, confirming efficacy in a larger sample size with extended follow-up. The safety profile was acceptable, with manageable toxicities. Clinical trial information: NCT02715284.

NR, not reached.