title: 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.
abstract: 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.
authors.affiliation: University of Turin, San Luigi Hospital, Orbassano (Turin), Italy. giorgio.scagliotti@unito.it
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Brian
authors.initials: B
authors.lastname: Schwartz
authors.forename: Reinhard
authors.initials: R
authors.lastname: Von Roemeling
authors.forename: Alan B
authors.initials: AB
authors.lastname: Sandler
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D012107:Research Design; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: C551661:ARQ 197; D047428:Protein Kinase Inhibitors; D011760:Pyrrolidinones; D011799:Quinazolines; D011804:Quinolines; D000069347:Erlotinib Hydrochloride; D019859:Proto-Oncogene Proteins c-met