A Phase 2 Study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer

Purpose: MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA. Methods: Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety. Results: Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-related AEs were grade 1 or 2. The only grade ³3 treatment related AEs were increased ALT and AST. Conclusion: Savolitinib was well tolerated, however in this small group of biomarker-selected patients we observed no evidence of anti-tumor activity. Trial Registration: www.clinicaltrials.gov NCT03592641. Registered on July 17th, 2018