Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study

作者：Filippo de Marinis, Tae Min Kim, L. Bonanno, S. Cheng, S-W Kim, Marcello Tiseo, Quincy Siu-Chung Chu, C. Proto, Adrian Gerold Sacher, Y.-H. Luo, S. Novello, Dapeng Hao, Christina S. Baik, Lyudmila Bazhenova, J.S. Lee, Byoung Chul Cho, J. Cadranel, Tuan Bao Diep, G. Metro, P R Narayanan, Yasuto Yoneshima, Javier de Castro, Clarissa Serodio da Rocha Baldotto, Christa Haugaard Nyhus, J.C.-H. Yang, Lecia Van Dam Sequist, Benjamin Philip Levy, R. Hartmaier, I. Igwegbe, L. Poole, Wei Xu, M-J. Ahn · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.04.003 · 被引用次数：53 · 研究领域：Lung Cancer Treatments and Mutations、Fibroblast Growth Factor Research、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

BACKGROUND: MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common. We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting. PATIENTS AND METHODS: Patients had EGFR-mutated, advanced NSCLC with MET overexpression and/or amplification. MET cut-offs were initially MET immunohistochemistry (IHC)3+/≥50% (3+ intensity in ≥50% of tumor cells) and/or FISH5+ (≥5 MET gene copies or MET/chromosome 7 centromere ratio ≥2), and increased to MET IHC3+/≥90% and/or FISH10+ after a preliminary analysis. Patients received oral savolitinib [300 mg twice daily (b.i.d.) or once daily (o.d.), or 600 mg o.d.] plus osimertinib 80 mg o.d., or savolitinib 300 mg b.i.d. plus placebo. A primary endpoint was investigator-assessed objective response rate (ORR) in patients with progression on first-line osimertinib and MET IHC3+/≥90% and/or FISH10+ status receiving savolitinib 300 mg b.i.d. plus osimertinib (primary efficacy population). Safety was analyzed in all patients receiving savolitinib plus osimertinib. RESULTS: Of the 365 patients treated, 341 received savolitinib plus osimertinib, with 80 of these included in the primary efficacy population. Investigator-assessed confirmed ORR in the primary efficacy population was 56.3% [95% confidence interval (CI) 44.7% to 67.3%]; the median duration of response (mDoR) was 7.1 month...