Background: Dostarlimab is an investigational, humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and PD-L2. GARNET (NCT02715284) is a phase 1 study assessing the antitumor activity and safety of dostarlimab monotherapy in patients with solid tumors. Methods: This multicenter, open-label, single-arm study is being conducted in 2 parts: dose escalation and expansion. Here we report on the 2 expansion cohorts that enrolled mismatch repair?deficient/microsatellite instability?high (dMMR/MSI-H) patients. Cohort A1 enrolled patients with advanced or recurrent dMMR/MSI-H endometrial cancer (EC), and cohort F enrolled patients with advanced or recurrent dMMR/MSI-H or POLε-hypermutated non-EC solid tumors, mainly gastrointestinal (GI) tumors (99 [93.4%] had GI tumors, including 69 [65.1%] with colorectal cancer). Patients received 500 mg IV of dostarlimab every 3 weeks for 4 cycles, then 1000 mg IV every 6 weeks until disease progression or discontinuation. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by RECIST v1.1. Here we report ORR and DOR, by individual cohort and as an overall population, in patients with dMMR tumors identified by immunohistochemistry testing. Results: For this interim analysis, an efficacy analysis was performed for the patients who had baseline measurable disease and ≥6 months of follow-up in the study (N = 209). The ORR was 41.6% (95% CI, 34.9%?48.6%) for the combined A1+F dMMR cohorts (Table). Responses were durable, and median DOR has not been reached in either cohort (median follow-up: cohort A1, 16.3 months; cohort F, 12.4 months). A total of 267 patients were included in the safety population (all patients who received ≥1 dose; cohort A1, N = 126; cohort F, N = 141). Treatment-related adverse events (TRAEs) were consistent across tumor types. Overall, the most frequently reported any-grade TRAEs were asthenia (13.9%), diarrhea (13.5%), and fatigue (11.2%). The most common grade ≥3 TRAEs were anemia (2.2%), lipase increased (1.9%), alanine aminotransferase increased (1.1%), and diarrhea (1.1%). No deaths were attributed to dostarlimab. Conclusions: Dostarlimab demonstrated durable antitumor activity in patients with dMMR solid tumors, with consistent antitumor activity seen across endometrial and nonendometrial tumor types. The safety profile was manageable, with no new safety signals detected. Most TRAEs were low grade and were similar across cohorts. Clinical trial information: NCT02715284

^aExact, 2-sided 95% CI for the binomial proportion.