Early clinical development of ARQ 197, a selective, Non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers

Alex A. Adjei, Brian Schwartz, Edward Garmey

Research output: Contribution to journalArticle

56 Scopus citations


Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non-ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/ metastatic non-small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non-squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcit-abine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens.

Original languageEnglish (US)
Pages (from-to)788-799
Number of pages12
Issue number6
StatePublished - Jun 1 2011



  • C-MET
  • EGFR
  • Epithelial growth factor inhibitor
  • Hepatocyte growth factor
  • Kinase receptor inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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