Evaluation of MET Detection Methods and Cutoffs in EGFR-Mutated Non-small Cell Lung Cancer Following Disease Progression on Osimertinib in the phase II SAVANNAH study

作者：Myung‐Ju Ahn, Filippo de Marinis, Byoung Chul Cho, Tae Min Kim, Susanna Yee-Shan Cheng, Silvia Novello, Claudia Proto, Sang‐We Kim, Jong Seok Lee, Giulio Metro, Lecia Van Dam Sequist, James Chih‐Hsin Yang, Wanning Xu, Aino Telaranta-Keerie, Alexander Todd, Gina D’Angelo, Ryan James Hartmaier, Laura S. Bonanno · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-26-0604 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

Purpose In the phase II SAVANNAH study (NCT03778229), savolitinib 300 mg BID plus osimertinib demonstrated a high objective response rate (ORR; 56%) in patients with EGFR-mutated advanced non-small cell lung cancer and high levels of MET overexpression and/or amplification following first-line osimertinib (primary efficacy population). We report earlier analyses from SAVANNAH leading to selection of the MET cutoffs used to define the primary efficacy population. Experimental Design MET overexpression was assessed by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). MET cutoffs were initially defined as 3+ staining in ≥50% of tumor cells (IHC3+/≥50%) and MET gene copy number ≥5 or MET:CEP7 ratio ≥2 (FISH5+), respectively. Results Confirmed ORR generally increased with increasing MET levels. MET IHC3+/≥90% and/or FISH10+ were identified as the optimal cutoffs. ORR: 49% (MET IHC3+/≥90% and/or FISH10+ subgroup) versus 9% (without MET IHC3+/≥90% and/or FISH10+); 32% (MET IHC3+/≥50% and/or FISH5+). Estimated prevalence was 62% for MET IHC3+/≥50% and/or FISH5+ status and 34% for MET IHC3+/≥90% and/or FISH10+ status. Conclusions Biomarker analyses from the SAVANNAH study found that MET IHC3+/≥90% and/or FISH10+ were the most appropriate cutoffs for savolitinib plus osimertinib treatment of EGFR-mutated, MET‑overexpressed and/or amplified, advanced NSCLC following progression on osimertinib. These MET cutoffs will be used to determine eligi...