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Background Mismatch repair-deficient (dMMRd) tumors are highly immunogenic and have shown significant responsiveness to immune checkpoint inhibitors. In this regard, we suggest a window of opportunity study of induction nivolumab in patients with surgically resectable dMMR endometrial cancer.Methods We conducted a multicenter, single-arm phase 2 trial. Inclusion criteria include clinical stage I-IIIC2, tumor specimen that demonstrates dMMR by immunohistochemistry or microsatellite instability. Patients were administered nivolumab 480 mg IV every 4 weeks for up to 6 months, followed by standard surgical resection and/or adjuvant therapy. Patients who had a clinical complete response after completion of nivolumab therapy would proceed without surgery and/or adjuvant therapy. The primary endpoint of the study is clinical complete response rate or pathological complete response rate after treatment of nivolumab. The Simon’s 2-stage minimax design was used. Target accrual is 15 patients in the first stage. If there are 4 or fewer responders, the study will stop for futility. In the second stage, an additional 15 patients will be enrolled, for a total of 30 patients. Efficacy is defined as more than 13 patients achieving a complete response.Results Of the 22 enrolled patients, 16 were evaluable for response. Thirteen patients (81.3%) achieved a clinical complete response, a finding that met the predefined primary endpoint for efficacy. Of the 13 patients who achieved a clinical complete response, 8 patients did not undergo surgery. The median follow-up was 12.2 months, and no disease recurrence was observed in any patient during this period. Grade 3 skin rash was reported in 2 patients, with no cases requiring permanent discontinuation of nivolumab. Pathogenic germline variants in a mismatch-repair gene were noted in 18.8% of the patients. Updated data on complete response rates, adverse events, and correlative analyses of the tumor microenvironment and genomic profiling will be presented at the meeting.Conclusions Nivolumab demonstrated a high rate of clinical complete responses in patients with dMMR endometrial cancer, including durable responses in those who avoided surgery. These findings support further evaluation of immunotherapy-based organ-preserving strategies in biomarker-selected endometrial cancer. Clinical trial information: NCT05795244.Trial Registration Clinical trial information: NCT05795244.Ethics Approval This study has been approved by the Institutional Review Board (IRB) at Severance Hospital, Yonsei University Health System (IRB number: 4-2023-0001). Permission to conduct this study was obtained from the administrators of all participating facilities.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal