Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS_24wks) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS_24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS_24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129