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.
Author(s): Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, von Pawel
J, Schwartz B, Von Roemeling R, Sandler AB.
Affiliation(s): University of Turin, San Luigi Hospital, Orbassano (Turin), Italy.
giorgio.scagliotti@unito.it
Publication date & source: 2012, Clin Lung Cancer. , 13(5):391-5
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.
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