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Clinical Trial
. 2024 Dec 9;56(1):29.
doi: 10.1007/s12029-024-01156-x.

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

Jingquan Jia  1 , Ashley Moyer  2 , Melissa Lowe  3 , Emily Bolch  3 , Jeremy Kortmansky  4 , May Cho  5 , Heinz-Josef Lenz  6 , Aparna Kalyan  7 , Donna Niedzwiecki  3   8 , John H Strickler  9   10
Affiliations
Clinical Trial

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

Jingquan Jia et al. J Gastrointest Cancer. .

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.

Keywords: MET amplification; EGFR antibody resistance; Metastatic colon cancer; Savolitinib.

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Conflict of interest statement

Declarations. Ethics Approval: Approval was obtained from the NCI Adult Central Institutional Review Board – Early Phase Emphasis. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Competing Interests: JJ: Consultant or advisory role: AstraZeneca, Cardinal Health Research funding or contracted research: Roche/ Genentech, AztraZeneca JS: Consultant or advisory role: Abbvie, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BMS, Daiichi-Sankyo, Eli Lilly, GE Healthcare, GSK, Incyte, Ipsen, Johnson and Johnson, Jazz Pharmaceuticals, Leap, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Sanofi, Taiho, Takeda, Xilio Therapeutics Stock options- Triumvira Immunologics Research funding or contracted research: Abbvie, Amgen, Apollo Therapeutics, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, Roche/ Genentech HJL: Stock options – Fulgent, 3 T Bioscience, Breakbio; Advisory Board-BMS, Adagene, 3 T Bioscience, Merck, Merck KG, Abbvie, Bayer; Research funding or contracted research: UM1CA186717, P30CA014089. MC: Honoraria-Amgen, AstraZeneca, Astellas, Bayer, Basilea, Bristol-Myers Squibb, Eisai, Exelixis, I-Mab, Ipsen, Incyte, Genetech/Roche, Natera, Pfizer, Seattle Genetics, Taiho, Tempus, QED; Employment – Replimune.

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