P-306 A phase II biopsy-driven study to identify biomarkers predictive of clinical response to second-line regorafenib in patients with metastatic colorectal cancer

Abstract

Introduction: A major challenge in advancing treatment formetastatic colorectal cancer (mCRC) is to identify biomarkers (BMs) predictive of response. We began a phase II investigator-initiated study to identify BMs predictive of response or resistance to regorafenib in blood and tumor tissue in patients with mCRC who failed first-line therapy (QCROC-06; NCT01949194). Regorafenib is an oral multikinase inhibitor that targets angiogenic, stromal and oncogenic kinases. The phase III CORRECT and CONCUR trials demonstrated that regorafenib monotherapy significantly increased overall survival in patients with mCRC1,2. Our objective is to determine predictive biomarkers to indicate which mCRC patients will likely benefit or be resistant to regorafenib. Methods: Patients with mCRC who failed first-line treatment (FOLFOX or FOLFIRI +/- bevacizumab) will receive regorafenib monotherapy in second-line and undergo a pre-treatment biopsy of a metastatic lesion site. A biopsy at disease progression is optional. The primary objective is to identify BMs of response or resistance in tumor tissue and blood. Secondary objectives include progression free survival, response rate, safety and feasibility of obtaining metastatic biopsies. Patients are recruited at 5 Canadian centers to collect 42 evaluable pre-treatment biopsies. Eighteen patients have been enrolled so far. Patients are largely recruited after participating in QCROC-01, a study to identify BMs of mCRC resistance to first-line therapy. The biopsy collected at resistance to first-line treatment in Q-CROC-01 is serving as the entry biopsy for QCROC-06. Genomic material will be isolated from all biopsies, and blood is collected for analysis of VEGF polymorphism and circulating tumor DNA. BMs will be identified using targeted and global profiling approaches.