HutchMed highlights publication of Phase III SACHI study results of savolitinib (Orpathys) and osimertinib (Tagrisso) for NSCLC in The Lancet

HutchMed highlights that results from the SACHI Phase III trial were published in The Lancet. SACHI is a Phase III study of the savolitinib (Orpathys) and osimertinib (Tagrisso ) combination for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with MET amplification after disease progression on first-line EGFR tyrosine kinase inhibitor (TKI) therapy.

In January 2025, the Independent Data Monitoring Committee (IDMC) of SACHI considered that the study had met the pre-defined primary endpoint of progression-free survival (“PFS”) in a planned interim analysis and, as a result, enrollment into the study has concluded. As of the interim analysis data cut-off of August 30, 2024, a total of 211 patients were randomized to receive the savolitinib and osimertinib combination (n=106) or chemotherapy (n=105). In the intention-to-treat (“ITT”) population, the median PFS assessed by investigator was 8.2 months (95% confidence interval [“CI”] 6.9–11.2) with savolitinib plus osimertinib, compared to 4.5 months (95% CI 3.0–5.4) with chemotherapy (hazard ratio [“HR”] 0.34; 95% CI 0.23–0.49; p<0.0001). The independent review committee (“IRC”) assessed median PFS was 7.2 vs 4.2 months, respectively (HR 0.40; 95% CI 0.28–0.59; p<0.0001).

The investigator-assessed objective response rate (“ORR”) was 58% in the savolitinib plus osimertinib arm compared to 34% for patients in the chemotherapy arm. The disease control rate (DCR) was 89% vs 67%, and the median duration of response (DoR) was 8.4 vs 3.2 months, respectively. The median time to response (TTR) was similar between two arms (1.4 vs 1.5 months). Overall survival (“OS”) data were still evolving and not mature at the time of the interim analysis, with only 37% and 43% OS maturity. At median OS follow-up duration of 17.7 months in the ITT population, savolitinib plus osimertinib arm reported median OS of 22.9 months vs 17.7 months in the chemotherapy arm (HR 0.84). 55 (52%) patients in the chemotherapy arm received subsequent MET inhibitor therapy after disease progression, with 45 (43%) crossing over to savolitinib-osimertinib and ten (10%) subsequently received MET inhibitor. In sensitivity analyses of OS to adjust for this crossover, the OS benefits of the savolitinib plus osimertinib arm were more significant, with HRs ranging from 0.24 to 0.62.

In the third-generation EGFR TKI–naïve subgroup population (i.e. patients previously treated with a first- or second-generation EGFR TKI), investigator-assessed median PFS was 9.8 vs 5.4 months (HR 0.34; 95% CI 0.21–0.56; p<0.0001). Efficacy outcomes in the third-generation EGFR-TKI–treated subgroup were comparable with those in the ITT population. In this subgroup, the investigator-assessed median PFS was 6.9 vs 3.0 months (HR 0.32; 95% CI 0.18–0.57; p<0.0001), and IRC-assessed median PFS was 6.9 vs 3.0 months (HR 0.32; 95% CI 0.18–0.58; p<0.0001).

The safety profile of the savolitinib and osimertinib combination was tolerable and no new safety signals were observed. Treatment-emergent adverse events (“TEAEs”) of Grade 3 or above occurred in 57% of patients in the savolitinib plus osimertinib arm compared to 57% (55 of 96) for patients in the chemotherapy arm. Common Grade ≥3 TEAEs (≥10% in either arm) included decreased neutrophil count (14% vs 26%), decreased white blood cell count (7% vs 13%), and anemia (4% vs 23%).

“The SACHI trial, now published in The Lancet, provides compelling evidence that savolitinib combined with osimertinib can transform outcomes for patients with EGFR-mutated NSCLC with MET amplification. These findings highlight the combination’s ability to address MET amplification, a critical resistance mechanism, offering clinically meaningful improvements for this challenging patient population,” said  Prof. Shun Lu, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, and co-leading Principal Investigator of the SACHI trial.

“We are particularly encouraged by the consistent benefits observed in patients previously treated with third-generation EGFR-TKIs, where savolitinib plus osimertinib offers a continued all-oral regimen, providing a convenient and well-tolerated solution for this underserved population.” Prof. Jie Wang of Cancer Hospital, Chinese Academy of Medical Sciences also served as co-leading Principal Investigator of the SACHI trial.

See- Lu S, Wang J et al Savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified non-small-cell lung cancer in China (SACHI): interim analysis of a multicentre, open-label, phase 3 randomised controlled trial. Lancet, Published Online January 13, 2026 DOI: 10.1016/S0140-6736(25)01811-2