ONC-2012-001: A single-arm phase II study of tivantinib (ARQ 197) plus cetuximab in EGFR inhibitor-resistant MET high patients (pts) with locally advanced or metastatic colorectal cancer (CRC) with wild-type KRAS.

TPS3661 Background: MET overexpression has been identified in 30-70% colorectal cancer (CRC) and activation of this pathway can be associated to resistance to cetuximab (Krumbach R et al, Eur J Cancer 41:1231-43, 2011). Tivantinib (ARQ 197) is a non-adenosine triphosphate (ATP)-competitive, oral inhibitor of the MET receptor tyrosine kinase. The ARQ 197-A-U252 phase I/II trial in wild-type KRAS metastatic CRC (mCRC) demonstrated that tivantinib in combination with irinotecan and cetuximab is well tolerated and showed encouraging antitumor activity, particularly in MET-high patients (pts) (Eng C et al, J Clin Oncol 31, 2013; suppl, abstr 3508). Additionally in the last years, the potential role of epidermal growth factor receptor inhibitors beyond progression in mCRC has been evaluated. Adding tivantinib to cetuximab is based on a strong rationale to improve outcome in cetuximab resistant MET-high mCRC pts. Methods: Enrollment in this single-arm, Simon 2-stage, phase II study (ONC-2012-001) has begun. Elig...