4038 Background: Linifanib (ABT-869), a novel potent and selective inhibitor of the VEGF and PDGF platelet-derived growth factor families of RTKs, is designed to inhibit angiogenesis, tumor growth, and metastasis. Methods: This was an open-label, multicenter trial of oral linifanib 0.25 mg/kg QD in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity. Key eligibility included unresectable or metastatic HCC; ≥1 prior systemic therapy; at least one measurable lesion by CT scan. Endpoints were progression free (PF) rate at 16 weeks (primary) and ORR, time to progression (TTP), time to radiographic progression (TTPr), OS (secondary). Results: 44 pts were enrolled from 09/07 to 08/08, 84% received no prior systemic therapy. Median age was 62 y (range 20-81). Most common linifanib-related AEs were fatigue (55%) and diarrhea (48%). Most common linifanib-related grade 3 or 4 AEs (NCI toxicity criteria) were hypertension (HT, 18%) and fatigue (14%). 68% of pts had dose interruptions due to AEs; most common reasons included HT (18%) and proteinuria (11%), which were reversible. 34% of pts required dose reductions due to AEs. As of 11/09, 4 pts (CP-A) remained on study. 27 pts had discontinued due to PD (clinical, radiographic, or AE related to PD), 8 due to AEs not related to PD, and 5 for other reasons. There was one death possibly related to linifanib (intracranial hemorrhage, Day 111, CP-B). Serum protein induced by vitamin K absence (PIVKA) was decreased in 11 of 33 evaluable pts on study and was associated with improved OS. Conclusions: Linifanib is clinically active in advanced HCC (C-PA), with an acceptable safety profile. A phase III study of linifanib vs sorafenib in this setting is ongoing. Point estimate (95% CI) CP-A n=38 CP-B n=6 All N=44 PF rate at 16 weeks (%) 34.2 (19.6, 51.4) 16.7 (0.4, 64.1) 31.8 (18.6, 47.6) ORR* (%) 7.9 (1.7, 21.4) 0 6.8 (1.4, 18.7) TTP** (mo) 5.4 (3.6, 14.1) 3.7 (0.7, NR) 3.7 (3.6, 7.3) TTPr** (mo) 5.4 (3.6, NR) NR (3.7, NR) 5.4 (3.6, NR) OS** (mo) 10.4 (8.4, 14.9) 2.5 (1.1, 4.5) 9.7 (6.3, 12.2) Abbreviation: NR, not reached. Results based on radiographic (central imaging center) and clinical (investigator) assessments. * Per RECIST. Responses confirmed on 2 visits >4 weeks apart. ** Estimated median. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Medigene Abbott Laboratories Bristol-Myers Squibb, GlaxoSmithKline, Merck