Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET -amplification ( MET amp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study.

作者：Shun Lu, Jie Wang, Nong Yang, Dongqing Lv, Lijuan Chen, Lin Wu, XingYa Li, Longhua Sun, Yongfeng Yu, Bo Jin, Lin Yang, Yubiao Guo, Haipeng Xu, Tienan Yi, Aiping Zeng, Xiaorong Dong, Jianhua Chen, Ziping Wang, Tony Mok, Weiguo Su, SACHI Study Group · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.17_suppl.lba8505 · 被引用次数：9 · 研究领域：Lung Cancer Treatments and Mutations、Cytokine Signaling Pathways and Interactions、Synthesis and biological activity

LBA8505 Background: Savo, a highly selective MET -TKI, combined with osi, may overcome acquired MET -driven resistance in EGFRm advanced NSCLC after PD on EGFR-TKIs. Here we report primary results of the prespecified interim analysis (IA) in SACHI study, comparing efficacy and safety of savo + osi with chemo in this disease setting. Methods: In this randomized, open-label, phase 3 study, 250 EGFRm and MET amp advanced NSCLC patients (pts) post PD on first-line EGFR-TKI were planned ( MET copy number ≥5 or MET /CEP7 ratio of ≥2.0 by FISH for pts with prior 1 st /2 nd generation [G] EGFR-TKI; MET copy number ≥10 for pts with prior 3 rd G EGFR-TKI); T790M negative after PD on 1 st /2 nd G EGFR-TKI was required. Eligible pts were randomly assigned (1:1) to receive savo 400 or 600 mg QD (for body weight of < 50, or ≥ 50 kg respectively) + osi 80 mg QD, or chemo (pemetrexed + carboplatin/cisplatin), stratified by brain metastases, prior use of 3G EGFR-TKI, and type of EGFR mutations. Crossover to savo + osi after IRC-PD was permitted for chemo group. The primary endpoint, PFS by investigator (INV) per RECIST 1.1, was hierarchically tested via a stratified log-rank test in 3G EGFR-TKI treatment-naïve set firstly, then in ITT set. This is a prespecified IA conducted via an independent data monitoring committee to assess efficacy superiority or sample size re-estimation. Results: From 15 Oct 2021 to 30 Aug 2024 (DCO for IA), 211 pts were randomized to receive savo + osi or chemo (n...