Rationale and Design of MARQUEE: A Phase III, Randomized, Double-Blind Study of Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Patients With Locally Advanced or Metastatic, Nonsquamous, Non-Small-Cell Lung Cancer

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• 作者：Giorgio V. Scagliotti ; Silvia Novello ; Joan H. Schiller ; Vera Hirsh ; Lecia V. Sequist ; Jean-Charles Soria ; Joachim von Pawel ; Brian Schwartz ; Reinhard Von Roemeling ; Alan B. S ; ler
• 关键词：Epidermal growth factor receptor ; Hepatocyte growth factor receptor ; MET ; Tyrosine kinase inhibitors
• 刊名：Clinical Lung Cancer
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：13
• 期：5
• 页码：391-395
• 全文大小：331 K

文摘

We present the rationale and design for MARQUEE, a phase III, randomized, double-blind, placebo-controlled study of ARQ 197 plus erlotinib versus placebo plus erlotinib in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer (NSCLC). The design of MARQUEE is based on preclinical data, the current understanding of the role of cellular N-methyl-N'-nitroso-guanidine human osteosarcoma (MNNG HOS) transforming gene (MET) in NSCLC, and clinical data from a randomized phase II study. The available evidence suggests that dual inhibition of MET and the epidermal growth factor receptor (EGFR) may overcome resistance to EGFR inhibitors. In the phase II study, the combination of tivantinib plus erlotinib significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus erlotinib in the subset of patients with nonsquamous histology, a population enriched for MET overexpression. The primary endpoint in MARQUEE is OS. Secondary and exploratory objectives include determination of PFS, OS in molecular subgroups (defined by EGFR and KRAS mutation status, amplification or overexpression of MET, and serum hepatocyte growth factor), and safety. All patients will be tested for biomarkers, and the results will provide a wealth of information on the role of tivantinib in treating nonsquamous NSCLC.