Background: Dostarlimab is a humanized anti–PD-1 monoclonal antibody that binds the PD-1 receptor, blocking interaction with ligands PD-L1 and PD-L2. The ongoing phase 1 GARNET study (NCT02715284) is evaluating dostarlimab in pts with advanced solid tumors. Here we present safety and efficacy data from cohort F. Methods: Cohort F of the GARNET trial enrolled pts with dMMR or POLEmut non-endometrial solid tumors; the majority were gastrointestinal (GI) in origin. Pts must have progressed per blinded independent central review (BICR) following prior systemic therapy for advanced disease and had dMMR status by local immunohistochemistry. Pts received 500 mg dostarlimab Q3W for 4 cycles and 1000 mg Q6W until discontinuation. Objective response rate (ORR) and duration of response (DOR) were assessed by BICR per RECIST v1.1. Pts were included in the efficacy analysis if they received ≥1 dose of dostarlimab, had measurable disease at baseline, and 6 mo of follow up. All pts who received ≥1 dose were included in the safety analysis. Results: 144 pts were included in the safety analysis, with 106 dMMR pts in the efficacy analysis (1 POLEmut pt with a confirmed PR was not included in this population). Of the 106 pts, 99 (93.4%) had GI tumors. Confirmed ORR in dMMR pts was 38.7% (95% CI: 29.4, 48.6), with a complete response rate of 7.5%. ORR was consistent across tumor type (Table). At the data cutoff, median duration of follow-up (n = 107; dMMR and POLEmut pts) was 12.4 months and median DOR was not reached. The Kaplan–Meier estimated probability of maintaining response at 12 and 18 months was 91.0% and 80.9% respectively. Treatment-related adverse events (TRAEs) were reported in 68.8% of pts; 8.3% of pts experienced at least 1 grade ≥3 TRAE. The most common was lipase increased in 2 (1.4%) pts. Treatment-related serious AEs (SAEs) were reported in 6 (5.5%) pts, and 2 pts (1.8%) discontinued dostarlimab due to a TRAE. No deaths were attributed to dostarlimab. Conclusions: Dostarlimab demonstrated durable antitumor activity in a cohort of dMMR solid tumor pts, the majority of whom had GI cancers. The safety profile was consistent with other cohorts in GARNET, with immune-related TRAEs infrequent and low grade. Clinical trial information: NCT02715284

*Exact, 2-sided 95% CI for the binomial proportion.

CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease.