Phase I study of PF-03446962 (anti-ALK-1 mAb) in hepatocellular carcinoma (HCC).

4121 Background: PF-03446962, a fully human IgG2 mAb against ALK-1 (Activin-Receptor Like Kinase-1, a specific TGF-β receptor) with anti-angiogenesis activity, showed a favourable safety profile and early signs of efficacy in a dose escalation study in patients (pts) with solid tumors. While the interplay between ALK-1 and VEGF-A is not fully elucidated, the clinical benefit observed in VEGF-TKI pre-treated pts supports ALK-1 acting as an escape mechanism after failure of VEGF blockade. Herein we report preliminary efficacy, safety and PK results from an expansion cohort in HCC pts who progressed after receiving at minimum sorafenib. Methods: Child-Pugh A HCC pts progressed on/intolerant to sorafenib. Tumor specimens (diagnostic and pre-PF-03446962) collected for IHC assessment of CD31, TGF-β, ALK-1 and cMET. Pts treated with 7 mg/kg PF-03446962 on Day 1, 29 and then q2 wks. Efficacy endpoints: Objective Tumor Response (OR) by RECIST, Disease Control Rate (DCR) at 12 wks, and Time To Progression (TTP). Se...