Results from the phase 3 SACHI study demonstrated that savolitinib, a highly selective MET-tyrosine kinase inhibitor (TKI), plus osimertinib improved efficacy and safety compared to chemotherapy among patients with epidermal growth factor receptor (EGFR)-mutated and MET-amplified advanced non-small cell lung cancer (NSCLC). 

These data were first presented by Shun Lu, MD, PhD, Shanghai Chest Hospital, Shanghai, China, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this open-label study, 211 patients who experienced disease progression after first-line treatment with an EGFR-TKI were randomized on a 1:1 basis to receive either 400 or 600 mg of savolitinib (based on body weight) plus 80 mg of osimertinib (n = 106) or chemotherapy (n = 105). Stratification was based on presence of brain metastases, prior use of third-generation EGFR-TKI, and type of EGFR mutation. Patients enrolled in the chemotherapy arm were permitted to crossover to the savolitinib plus osimertinib arm upon disease progression. The primary end point was investigator-assessed progression-free survival (PFS). Key secondary end points included median PFS by independent review, objective response rate (ORR), duration of response, overall survival (OS), and safety. 

At analysis, investigator-assessed median PFS was 8.2 months in the savolitinib plus osimertinib arm and 4.5 months in the chemotherapy arm. Median PFS via independent review was 7.2 months and 4.2 months, respectively. The ORR was 63.2% in the savolitinib plus osimertinib arm and 36.2% in the chemotherapy arm. Median duration of response was 9.7 months in the savolitinib plus osimertinib arm and 4.3 months in the chemotherapy arm and 52.4% of patients crossed over from the chemotherapy arm to receive either savolitinib plus osimertinib or another MET inhibitor. Median OS was 22.9 months and 17.7 months, respectively. Grade ≥3 treatment-related adverse events occurred in 56.6% of patients in the savolitinib plus osimertinib arm and 57.3% of patients in the chemotherapy arm. Patients in the savolitinib plus osimertinib arm experienced fewer incidences of hematologic events. 

As Dr Lu et al concluded, savolitinib plus osimertinib “is a potential new treatment option for this genomically defined population.” 

Source: 

Lu S, Wang J, Yang N, et al. Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA8505