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-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs.
Conclusion: Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.
Trial registration: Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.
Keywords: MET amplification; EGFR antibody resistance; Metastatic colon cancer; Savolitinib.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.