4577 Background: Brivanib is an orally available dual inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signaling. FGF pathway activation is of increasing importance in the setting of liver fibrosis and HCC. This phase II study aimed to assess the efficacy and safety of brivanib in patients (pts) with unresectable, locally advanced or metastatic HCC who had received either no prior systemic therapy (Cohort A) or one prior regimen of angiogenesis inhibitor (Cohort B). Methods: Eligible pts had biopsy-proven HCC or had radiological evidence of HCC and were serology positive for Hep B or C with alpha fetoprotein levels ≥ 400 μg/L. Pts received brivanib 800 mg qd. Efficacy endpoints included OS, PFS, TTP, ORR, and DCR. Safety was assessed throughout the study. Serum levels of a biomarker, Collagen IV (a component of the basement membrane of blood vessels), were measured on day 1, weeks 3 and 6, and at end of treatment. Results: Interim results are reported. From December 2006 to October 2008, 96 patients were enrolled (Cohort A: 55 pts; Cohort B: 41 pts). In Cohort B, 38 pts had failed sorafenib and 3 had failed thalidomide. In Cohort A, median OS (95% CI) was 10 (6.8,-) months. Most frequently reported grade 3/4 AEs were fatigue (16%), AST elevation (19%), and hyponatremia (41%) in Cohort A and hypertension (7.3%), diarrhea (4.9%), and headache (4.9%) in Cohort B. 24 pts died in Cohort A and 5 pts in Cohort B, none were considered treatment-related. Treatment-induced reductions in serum Collagen IV appear to correlate with long term outcome (PFS and OS). Conclusions: Brivanib has activity as both first-line and second-line post-sorafenib systemic treatment in HCC. Collagen IV, a novel serum angiogenic biomarker, appears to be associated with outcome. [Table: see text] [Table: see text]