HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

Abstract
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 gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens.
AuthorsAlex A Adjei, Brian Schwartz, Edward Garmey
JournalThe oncologist (Oncologist) Vol. 16 Issue 6 Pg. 788-99 ( 2011) ISSN: 1549-490X [Electronic] England
PMID21632449 (Publication Type: Journal Article)
Chemical References
  • ARQ 197
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyrrolidinones
  • Quinazolines
  • Quinolines
  • Receptors, Growth Factor
  • Hepatocyte Growth Factor
  • Irinotecan
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Cetuximab
  • Camptothecin
Topics
  • Animals
  • Antibodies, Monoclonal (administration & dosage, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents (administration & dosage, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Camptothecin (administration & dosage, analogs & derivatives, therapeutic use)
  • Cetuximab
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (administration & dosage, therapeutic use)
  • ErbB Receptors (antagonists & inhibitors, metabolism)
  • Erlotinib Hydrochloride
  • Hepatocyte Growth Factor (metabolism)
  • Humans
  • Irinotecan
  • Mice
  • Neoplasms (drug therapy)
  • Proto-Oncogene Proteins c-met (antagonists & inhibitors)
  • Pyrrolidinones (administration & dosage, therapeutic use)
  • Quinazolines (administration & dosage, therapeutic use)
  • Quinolines (administration & dosage, therapeutic use)
  • Randomized Controlled Trials as Topic
  • Receptors, Growth Factor (antagonists & inhibitors)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: