A first-in-human phase I study of sEphB4-HSA (sEphB4) with expansion in hepatocellular (HCC) and cholangiocarcinoma (CCA).

285Background: EphrinB4, a receptor kinase, is associated with stage and survival in epithelial cancers. sEphB4 is a fusion protein of soluble EphB4 and albumin. sEphB4 binds to EphrinB2, a protein expressed in tumor cells and vessels, and blocks bidirectional signaling. sEphB4 downregulates the PI3K/AKT/mTOR pathway, inhibits angiogenesis, and promotes recruitment of cytotoxic T cells and NK cells. MTD was not reached during dose escalation. The RP2D was 10 mg/Kg weekly. Here we report the results of the expansion cohorts in HCC and CCA. Methods: The study evaluated the safety, PK, PD and efficacy of sEphB4 in pts with advanced solid tumors in a 3+3 design with expansion at the RP2D in 7 solid tumors including HCC and CCA. Pts received sEphB4 10 mg/kg IV weekly in 28-day cycles. Eligibility included ECOG 0-1, Child-Pugh score ≤ 7, platelets > 50,000, AST/ALT ≤ 3xULN, serum bilirubin ≤ 1.5mg/dL and no uncontrolled hypertension. Results: 29 pts were treated: 17 HCC and 12 biliary cancers (8 CCA and 4 gallb...