First-Line Savolitinib/Osimertinib Improves PFS in MET+ NSCLC

The combination of savolitinib (Orpathys) and osimertinib (Tagrisso) significantly prolonged progression-free survival (PFS) compared with osimertinib alone in treatment-naive patients with EGFR-mutated, MET-overexpressing non–small cell lung cancer (NSCLC), according to results from the phase 3 SANOVO trial (NCT05009836) conducted in China.¹

The trial met its primary end point, with a statistically significant and clinically meaningful PFS benefit observed with the combination in both the high-MET and intention-to-treat (ITT) populations. While follow-up remains ongoing, an improvement in overall survival (OS), a secondary end point, was also reported in both populations.

The safety profile of the combination was reported to be consistent with the known safety profiles of each individual agent, and no new safety signals were identified. Full results are expected to be presented at a future medical meeting.

“Co-occurring MET overexpression in treatment-naive EGFR-mutated NSCLC often compromises the long-term durability of EGFR-[tyrosine kinase inhibitor; TKI] monotherapy. The positive findings from SANOVO demonstrate that addressing both pathways upfront with an all-oral, biomarker-directed regimen offers a powerful new approach for these patients whose tumors have MET overexpression,” Yi-Long Wu, of Guangdong Provincial People’s Hospital and principal investigator of SANOVO, stated in a news release.¹ “By combining [savolitinib] with [osimertinib], we have observed a clear clinical benefit that could reshape primary treatment strategy for this distinct patient population.”

SANOVO Trial Design

SANOVO is a blinded, randomized, controlled phase 3 study conducted in China that has enrolled previously untreated patients with locally advanced or metastatic NSCLC harboring activating EGFR mutations (exon 19 deletion or L858R) and MET overexpression.² A total of 326 patients were randomized 1:1 to receive osimertinib at 80 mg once daily plus either savolitinib or placebo, dosed at 300/200 mg twice daily based on body weight.

The primary end point is investigator-assessed PFS. Additional end points include PFS by independent review committee, OS, objective response rate, duration of response, disease control rate, time to response, and safety.

Building on Prior Data

The SANOVO findings extend a growing body of evidence supporting dual inhibition of the EGFR and MET pathways in EGFR-mutated NSCLC. MET overexpression or amplification can contribute to tumor growth and metastatic progression and is a recognized mechanism of resistance to EGFR TKI therapy.³

The combination of savolitinib and osimertinib has previously demonstrated activity in patients whose EGFR-mutated tumors develop MET-driven resistance following treatment with an EGFR TKI. In the phase 3 SACHI trial (NCT05015608), which supported the combination’s approval in China, treatment with the combination significantly improved PFS compared with chemotherapy in patients with EGFR-mutated, MET-amplified NSCLC following EGFR TKI treatment. Among the ITT population, median PFS was 8.2 months with savolitinib plus osimertinib vs 4.5 months with chemotherapy (HR, 0.34; P <.0001).⁴

More recently, the global phase 3 SAFFRON trial (NCT05261399) reported positive results for savolitinib plus osimertinib in patients with EGFR-mutated, MET-overexpressing or MET-amplified NSCLC whose disease had progressed on osimertinib. The combination significantly improved both PFS and OS compared with platinum-based chemotherapy, further supporting MET-directed treatment as a strategy for osimertinib-resistant disease.

Unlike the SACHI and SAFFRON studies, SANOVO is evaluating the combination upfront, before patients received systemic therapy. As such, the findings potentially expand the role of savolitinib plus osimertinib from a treatment strategy for MET-mediated resistance to a biomarker-directed first-line approach for patients whose tumors harbor both EGFR mutations and MET overexpression.

REFERENCES

1. HUTCHMED Announces SANOVO Trial Demonstrated Significant Progression-Free Survival Benefit of ORPATHYS^® Plus TAGRISSO^® in Treatment-Naïve Patients with MET-Overexpressing EGFR-mutated Lung Cancer in China. News release. August 31, 2026. Accessed September 1, 2026. https://tinyurl.com/58f2catm

2. Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/​MET+ Locally Advanced or Metastatic NSCLC (SANOVO). ClinicalTrials.gov. Updated June 10, 2026. Accessed September 1, 2026. https://clinicaltrials.gov/study/NCT05009836

3. Wu JJ, Zheng ZR, Lo TH, Chu CH, Chen KC, Chang GC. Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma. JTO clinical and research reports. doi:10.1016/j.jtocrr.2025.100832

4. Lu S, Wang J, Yang N, et al. 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. J Clin Oncol. 2025;43(17_suppl). doi:10.1200/jco.2025.43.17_suppl.lba8505