A phase II study of ramucirumab as first-line monotherapy in patients (pts) with advanced hepatocellular carcinoma (HCC).

Abstract

4083 Background: Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to HCC pathogenesis. Ramucirumab (IMC-1121B) is a recombinant human monoclonal antibody that binds to the extracellular domain of the VEGF receptor 2 (VEGFR-2). There is a compelling rationale for antiangiogenic (and specifically anti-VEGFR-2) therapy in HCC. Methods: Pts with advanced HCC received ramucirumab 8 mg/kg IV every (q) 2 weeks until disease progression or intolerable toxicity. Eligibility included no prior systemic therapy, Child-Pugh (C-P) A-B cirrhosis, ECOG PS 0-1, CLIP score 0-3, bilirubin ≤ 3 mg/dL, transaminases ≤ 5X ULN, Cr ≤ 2 mg/dL and platelets ≥ 75K. Tumor evaluations were q6 weeks. The primary endpoint was progression-free survival (PFS). Other endpoints were overall survival (OS), response rate, safety, pharmacokinetic (PK)/pharmacodynamic (PD) profiles, and immunogenicity of ramucirumab. Results: 43 pts were enrolled; 42 received therapy. Pts were predominantly male (81%), C-P A (74%), ECOG PS 0 (43%) or 1 (55%), and HCV-infected (49%). Most had extrahepatic disease (76%), BCLC stage C (83%), and 17% had macrovascular invasion. Median PFS was 4.3 months (m) and 4.0 m for pts with BCLC C (4.2 m for pts with C-P A, 2.8 m for pts with C-P B cirrhosis). 3 pts (7%) with extrahepatic disease and BCLC C had partial response, and 18 (43%) had stable disease (50% disease control rate). The most frequent adverse events (AEs) were fatigue (62%), headache (38%), and hypertension (HTN) (38%). Serious AEs included fatigue (10% grade [G] 3), gastrointestinal (GI) bleeding (7% G3; 2% G5), HTN (12% G3; 2% G4), infusion-related reactions (5% G3), and headache (2% G3). Cmin concentrations were above the target trough concentration (20 mg/mL) for the entire treatment period; evaluation through cycle 13 suggests no long-term accumulation of ramucirumab when administered q2 weeks. Conclusions: Ramucirumab confers moderate disease control in advanced, sorafenib-naive HCC. The treatment was well tolerated for most patients; serious AEs included GI bleeding, infusion- related reactions and HTN. Updated data on clinical efficacy and PD profiles will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems Bayer, Genentech, ImClone Systems Lilly