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Review
. 2022 Dec 12;14(24):6122.
doi: 10.3390/cancers14246122.

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration-A Narrative Review

Xiaokuan Zhu  1 , Yao Lu  2 , Shun Lu  1
Affiliations
Review

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration-A Narrative Review

Xiaokuan Zhu et al. Cancers (Basel). .

Abstract

Non-small cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Savolitinib (Orpathys®) is highly selective mesenchymal epithelial transition (MET)-tyrosine kinase inhibitor (TKI), which is conditionally approved in China for advanced NSCLC with MET exon 14 skipping mutations (METex14). This article summarizes the clinical development of savolitinib, as a monotherapy in NSCLC with METex14 mutation and in combination with epidermal growth factor receptor (EGFR) inhibitor in post EGFR-TKI resistance NSCLC due to MET-based acquired resistance. Preclinical models demonstrated anti-tumor activities in MET-driven cancer cell line and xenograft tumor models. The Phase Ia/Ib study established an optimized, recommended phase II dose in Chinese NSCLC patients, while TATTON study of savolitinib plus osimertinib in patients with EGFR mutant, MET-amplified and TKI-progressed NSCLC showed beneficial efficacy with acceptable safety profile. In a pivotal phase II study, Chinese patients with pulmonary sarcomatoid carcinoma, brain metastasis and other NSCLC subtype positive for METex14 mutation showed notable responses and acceptable safety profile with savolitinib. Currently, results from ongoing clinical trials are eagerly anticipated to confirm the efficacious and safety benefits of savolitinib as monotherapy and in combination with EGFR-TKI in acquired resistance setting in advanced NSCLC and its subtypes with MET alterations.

Keywords: EGFR; MET aberrations; non-small cell lung cancer; savolitinib; tyrosine kinase inhibitor.

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Conflict of interest statement

Yao Lu is an employee of AstraZeneca and works as a medical advisor in AstraZeneca, China.

Figures

Figure 1
Figure 1
Exploration of MET as oncogene and the journey leading to the development of MET–TKI. 1 Based on overall NSCLC population. 2 Based on treatment-naïve NSCLC population. 3 Based on EGFR-positive treatment-naïve NSCLC population.
Figure 2
Figure 2
Chemical structure of Savolitinib.
Figure 3
Figure 3
Key milestones and clinical trials in the development of savolitinib for non-small cell lung cancer.
See this image and copyright information in PMC

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