Background: There is a high unmet medical need for the treatment of patients [pts] with microsatellite stable [MSS], recurrent, metastatic, endometrial cancer [EC]. We reported encouraging preliminary antitumor activity with the triple combination of COM701 + BMS-986207 + nivolumab in patients with platinum resistant epithelial ovarian cancer [1]. COM701 is a novel, 1st-in-class immune checkpoint inhibitor [ICI] that binds to PVRIG, a DNAM-1 axis member, leading to activation of T-and NK-cells; BMS-986207 is an ICI of TIGIT. Nivolumab is an ICI of PD-1. We hypothesized that in pts with EC, the triple combination would demonstrate antitumor activity with a favorable safety and tolerability profile. We present encouraging preliminary results. Methods: As part of an expansion cohort, we enrolled 9 patients [pts] with EC. All pts received COM701 20 mg/kg + BMS-986207 480 mg + nivolumab 480 mg all IV Q4W. Primary objectives were safety/tolerability, with secondary objective of antitumor activity in pts with EC. Key inclusion criteria: Age ≥ 18 yrs, measurable disease, MSS by IHC or genomic testing, ≤2 prior systemic cytotoxic therapies, prior PD-1/PD-L1 permissible. Key exclusion criteria: prior receipt of anti-PVRIG, anti-TIGIT. Investigator assessed responses were per RECIST v1.1, safety per CTCAE v5.0. Results: Median age 71yrs, median of 2 prior lines of therapy, prior PD-1/PD-L1 3/9 [33%]. All pts received prior cytotoxic therapy. Objective response rate (ORR) 2/9 [22%] pts; 2 pts with SD. Disease control rate [CR + PR + SD] 4/9 [44%]. There were 2 pts with confirmed PR; 1 of these pts was refractory to prior receipt of lenvatinib + pembrolizumab [best response assessment of progressive disease]. Treatment related AEs were reported in 6/9 [67%] pts, the majority 4/6 [67%] were Grade 1 [1 pt each with chills, pyrexia, back pain and pruritus, lipase increased]. No new safety signals are reported. Conclusions: The combination of COM701 + BMS-986207 + nivolumab demonstrates encouraging preliminary signal of antitumor activity in pts with EC including in a pt refractory to prior exposure to lenvatinib + pembrolizumab. The triplet combination has a favorable safety/tolerability profile. Additional data analyses and pt follow up are ongoing and will be presented at the conference. Data extract 01/24/2023. 1. Moroney JW, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022) 16 (suppl_1): 100104-100104. 10.1016/iotech/iotech100104. Clinical trial information: NCT04570839.