Introduction Mismatch repair deficient endometrial cancer (MMRd-EC) is a subtype of endometrial carcinoma which exhibits aggressive characteristics and poor prognosis. MMRd tumors are known to be highly immunogenic and of great interest for immune checkpoint inhibitor. There is lack of data regarding the efficacy of nivolumab as induction monotherapy in completely resectable MMRd-ECs . In this regard, we suggest a window of opportunity study of induction PD-1 blockade (nivolumab) in patients with surgically resectable MMRd-EC .

Methods This multi-center, non-randomized, open-label Phase II study plans to enroll 30 patients with surgically resectable MMRd-EC. Additional inclusion criteria include clinical stage I-IIIC2, tumor specimen that demonstrates MMRd by immunohistochemistry or microsatellite instability as demonstrated by NGS or PCR. Exclusion criteria include multiple primary cancers, residual adverse effects of prior therapy or history of severe hypersensitivity to any antibody products . Patients will receive nivolumab at a dose of 480 mg IV, every 4 weeks as induction therapy for six cycles. Subsequently, patients will undergo surgery and/or receive adjuvant treatment following standard institutional guidelines. The primary endpoint is complete response rate of PD-1 blockade and surgery. Secondary endpoints include objective response rate, progression-free survival, overall survival, and adverse events. Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers.

Current Trial Status Open enrollment period: Dec/2022, to Dec/2024. The Target number: 30 patients. The study intends to provide valuable insights into the efficacy and safety of nivolumab as induction therapy for surgically resectable MMRd-EC.