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

Jingquan Jia, Ashley Moyer, Melissa Lowe, Emily Bolch, Jeremy Kortmansky, May Cho, Heinz Josef Lenz, Aparna Kalyan, Donna Niedzwiecki, John H. Strickler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number29
JournalJournal of Gastrointestinal Cancer
Volume56
Issue number1
DOIs
StatePublished - Dec 2025

Keywords

  • EGFR antibody resistance
  • MET amplification
  • Metastatic colon cancer
  • Savolitinib

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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