You are here
A multicenter, randomized, double-blind, phase III study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR).
Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title:
General Poster Session, Gastrointestinal (Noncolorectal) Cancer
J Clin Oncol 30, 2012 (suppl; abstr TPS4146)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Blockade of vascular endothelial growth factor (VEGF) signaling in HCC has been shown in preclinical models with monoclonal antibodies and small molecule multikinase inhibitors, and in clinical trials with SOR, to have anti-tumor activity and improve survival. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of the VEGF ligand to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. In a single-arm, Phase 2 study of RAM as 1st-line monotherapy in 42 pts with advanced HCC (Zhu, ILCA 2010, abstr. O-033), preliminary results included median progression-free survival (PFS) of 4 months (m), time to progression (TTP) of 4.2 m, overall survival (OS) of 12 m and disease control rate of 70% (best overall response: 10% partial response, 60% stable disease). Methods: Pts with HCC with disease progression during or following 1st-line therapy with SOR (or who were intolerant to SOR) are randomized 1:1 to receive RAM (8 mg/kg) or PBO once every 2 weeks, with BSC, until disease progression or intolerable toxicity. Eligibility includes prior SOR as 1st-line systemic treatment for HCC, Child-Pugh A, B7 or 8 cirrhosis, ECOG PS 0-1, bilirubin < 3 mg/dL, transaminases ≤ 5 × upper limit of normal (ULN), creatinine ≤ 1.2 × ULN, and platelets ≥ 75×103/µL. The primary endpoint is OS. Secondary endpoints include PFS, best objective response rate, TTP, patient-reported outcome measures of disease-specific symptoms and health-related quality of life, safety, and RAM pharmacokinetics, pharmacodynamics, and immunogenicity. With 544 patients, this study is designed to detect an increase in OS (median 6 m with PBO to 8 m with RAM; 1-sided α= 2.5%, 85% power). As of 18 January 2012, approximately 52% of planned pts have been randomized. The IDMC reviewed this study on 21 June and 3 November 2011 and recommended the study to continue unmodified.
Abstracts by Andrew X. Zhu:
A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: 376
A randomized, double-blind, placebo-controlled phase III study of ramucirumab versus placebo as second-line treatment in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein following first-line sorafenib (REACH-2).Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: TPS478
Emibetuzumab plus ramucirumab: Simultaneous targeting of MET and VEGFR-2 in patients with advanced hepatocellular cancer in a phase 1b/2 study.Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: 300
Educational Book Articles by Andrew X. Zhu:
Presentations by Andrew X. Zhu:
- Meeting: 2012 ASCO Annual Meeting