Receptor Kinase Inhibitors Target NSCLC
- PDF / 82,649 Bytes
- 3 Pages / 612.28 x 790.87 pts Page_size
- 43 Downloads / 250 Views
IN THOUGHT ALERT
ª 2011 Wolters Kluwer Pharma Solutions. All rights reserved.
Receptor Kinase Inhibitors Target NSCLCy Two Antibodies and a Small-Molecule MET Inhibitor David Yee inThought Research, Wolters Kluwer Pharma Solutions, Yardley, PA, USA
Abstract
Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo). Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab. Enrollment has been stopped in one of two necitumumab phase III trials because of safety concerns. Ramucirumab is an anti-VEGFR2 mAb targeting the same pathway as bevacizumab. Although the phase II safety data for ramucirumab appear better than the data for necitumumab, fewer phase III data are available. Tivantinib is a highly selective, orally available MET tyrosine kinase inhibitor. MET is overexpressed in 61% of NSCLC cases. Although tivantinib is the last of the three agents discussed here to enter phase III, its phase II results are the most robust.
Three targeted therapies have been approved by the US FDA for the treatment of non-small cell lung cancer (NSCLC): AstraZeneca’s gefitinib (Iressa) in 2003, OSI/Astellas and Genentech/Roche’s erlotinib (Tarceva) in 2004, and Genentech/ Roche’s bevacizumab (Avastin) in 2006. No targeted therapy has been added to this armamentarium in more than 4 years. This lack of approval has not been for lack of effort. The NSCLC programs of AstraZeneca’s vandetanib and Pfizer’s figitumumab and sunitinib all reached phase III before being discontinued in October 2009, March 2010, and September 2010, respectively. Past disappointments notwithstanding, a considerable number of phase III candidates are still in the running. Previous inThought Research Reports (dated August 5, 2010,[1] August 17, 2010,[2] and November 4, 2010[3]) highlighted ImClone, BristolMyers Squibb, and Merck Serono’s cetuximab (Erbitux); Onyx and Bayer’s sorafenib (Nexavar); Boehringer Ingelheim’s afatinib (Tovok) and intedanib (Vargatef); and Pfizer’s crizotinib. This report examines three additional receptor tyrosine kinase inhibitors that have reached phase III development.
1. Necitumumab (IMC-11F8) ImClone and Bristol-Myers Squibb’s necitumumab is a fully human IgG1 monoclonal antibody (mAb) that binds to the epidermal growth factor receptor (EGFR, erbB1), thus sharing the same target as the chimeric mAb cetuximab, which is already approved for colorectal cancer and for head and neck cancer. Cetuximab is also in phase III trials for NSCLC. ImClone has initiated two multicenter, randomized, openlabel phase III trials of necitumumab as first-line treatment for stage IV NSCLC. INSPIRE (A Randomized, Multicenter, Open-Label Phase 3 Study of Pemetrexed-Cisplatin Chemotherapy Plus Necitumumab [IMC-11F8] Versus Pemetrexed-Cisplatin Chemothera
Data Loading...
