Background: Angiogenesis has a role in endometrial cancer (EC) progression and prognosis. Single agent bevacizumab had a response rate (RR) of 13% and 6 month progression-free survival of 40% in recurrent EC with 1-2 prior cytotoxics. ALK1 is selectively expressed on activated endothelial cells unlike constitutively expressed VEGFR2. ALK1 pathway is essential for vascular morphogenesis and the formation of functional capillary networks in developing vasculature. EC vasculature has variable ALK1 expression. Dalantercept (Dal), a first-in-class ALK1 receptor fusion protein, binds to BMP9/BMP10 and prevents ALK1 pathway activation. Methods: A 2-stage design was used to estimate number of pts with persistent/recurrent EC who survived progression-free without receiving non-protocol therapy (TPFS) for at least 6 mos and number of pts who had objective tumor response (ORR) and determine toxicity of Dal 1.2 mg/kg SC Q3W. Recurrent/persistent epithelial EC, measurable disease, and 1- 2 prior chemotherapy lines were required. Biologic adjuvant therapy was permitted. Results: 28 pts ages 47-79 years were enrolled. G1/2 Endometrioid (n=9, 32%) and serous (n=15, 54%) tumors were most common. 82% of pts had 1 prior regimen. Pts received 1-12 cycles of Dal; 13 pts (46%) received ≤2 cycles. Most common adverse events (AE) regardless of attribution were fatigue, anemia, constipation, and limb edema. Grade (G) 3 and 4 AEs occurred in 39% and 4% of pts. There was 1 G 5 AE possibly Dal associated: gastric hemorrhage in pt with history of radiation fibrosis/small bowel obstruction. All pts are off study treatment: 24 for disease progression (PD), 1 consent withdrawal, 2 for toxicity, 1 for death. By RECIST 1.1: ORR was 0%; stable disease 57%, PD 39%, and indeterminate 4%. 11% of pts had TPFS > 6 mos; median PFS 2.1 mos (90% CI: 1.4-3.2) and median OS 9.4 mos (90% CI: 8.9-11.7). Conclusions: Dal has insufficient single agent activity in recurrent EC to warrant further investigation at this dose/schedule. Studies of IHC expression of VEGF, FGF, PDGF, TGF-β, ALK1, CD105, ALK1 gene expression, plasma concentration of VEGF, BMP9, BMP10, and ALK1 via ELISA are ongoing. Clinical trial information: NCT01642082.