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Phase 3 SACHI interim analysis: savolitinib plus osimertinib reported to prolong PFS versus chemotherapy in MET-amplified, EGFR-mutant NSCLC

In this interim analysis, in Chinese patients with EGFR mutation-positive NSCLC and MET amplification after first-line EGFR TKI failure, investigators reported prolonged investigator-assessed PFS with the combination versus chemotherapy.

  • Shun Lu, MD; Jie Wang, MD; Nong Yang, MD; Dongqing Lv, MD; Lijuan Chen, MD; Lin Wu, MD; et al.

  • January 13, 2026

  • The Lancet
  • Volume 407, Issue 10526, Pages 375–387
  • 10.1016/S0140-6736(25)01811-2

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Evidence before this study

PubMed was searched from database inception to April 21, 2025, using the search terms “((lung cancer) AND (EGFR)) AND (MET)”, filtered for clinical trials and then sorted to capture articles reporting on EGFR tyrosine kinase inhibitor (TKI) MET combination treatments for patients with advanced, MET-amplified, EGFR mutation-positive non-small-cell lung cancer (NSCLC) with progression after EGFR TKI therapy. An additional search of the American Society of Clinical Oncology (ASCO) abstracts database was conducted using the same search terms and time frame. These searches yielded a total of 12 relevant articles and eight ASCO abstracts describing findings from 13 distinct clinical trials, all published since 2013. All clinical trials were early phase (1, 1b, or 2), and predominantly single-arm, open-label, and global studies; three were randomised. The patient populations of the studies were highly heterogeneous with respect to the previous EGFR TKI treatment and line of therapy associated with treatment failure, the method of identifying MET expression status (ie, gene dysregulation vs immunohistochemistry-based tumour cell MET protein expression), and requirement for MET mutation as a study entry criterion. Patients with MET amplification or MET tumour tissue overexpression with progression after first-line EGFR TKI were the focus of just three studies (, [INSIGHT 2], and [SAVANNAH]). Of the three randomised trials, one compared erlotinib with or without emibetuzumab in patients with acquired resistance to erlotinib (any line of therapy) and tumour MET overexpression. A second compared erlotinib with or without onartuzumab in patients with recurrent NSCLC who had two or three previous lines of therapy. Although neither EGFR nor MET dysregulation were required at baseline, findings were analysed separately according to MET immunohistochemistry expression and EGFR mutation status. The third trial was a randomised subset of the SAVANNAH trial that evaluated outcomes with savolitinib with or without osimertinib, overall and according to the presence of brain metastases. The absence of evidence comparing study drug combinations with standard of care in this field highlights the need for efficacious and well-tolerated options to address resistance to EGFR TKI therapy, which invariably develops in patients with EGFR mutation-positive NSCLC.

Added value of this study

The protocol-specified interim analysis of the SACHI study met its primary endpoint of statistically significant prolongation of investigator-assessed progression-free survival (PFS) with savolitinib in combination with osimertinib versus chemotherapy in Chinese patients with EGFR mutation-positive NSCLC and MET amplification after failure of first-line EGFR TKI, in both the third-generation EGFR TKI-naive and intention-to-treat populations. As a result, an independent data monitoring committee recommended termination of study enrolment for superior efficacy. Savolitinib plus osimertinib also showed improvements in independent review committee-assessed PFS and tumour response versus chemotherapy in both analysis populations, and conferred efficacy benefits in patients with previous first-line third-generation EGFR TKI exposure. The safety profile of savolitinib plus osimertinib was well tolerated and similar to that reported in early-phase studies and with proportionately fewer haematological adverse events than observed with chemotherapy.

Implications of all the available evidence

SACHI is the first randomised phase 3 trial to support the efficacy of MET inhibition in patients with acquired MET amplification after progression on previous EGFR TKIs. Savolitinib plus osimertinib has potential to provide an oral treatment option that directly targets MET amplification-mediated resistance, which occurs in about a fifth of patients with EGFR mutation-positive NSCLC treated with EGFR TKIs.

Source: The Lancet

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