Savolitinib Combo Boosts PFS in First-Line EGFR-Mutant NSCLC Trial

Savolitinib (Orpathys) plus osimertinib (Tagrisso) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs osimertinib alone as first-line treatment for patients with locally advanced or metastatic EGFR-mutant, MET-overexpressing non–small cell lung cancer (NSCLC), according to a news release from HUTCHMED on the phase 3 SANOVO trial (NCT05009836) in China.¹ The benefit was observed in both the high MET and intention-to-treat (ITT) populations, and the combination also showed an encouraging overall survival (OS) trend.

What did the SANOVO trial show?

The all-oral combination of savolitinib plus osimertinib produced a statistically significant and highly clinically meaningful improvement in the primary end point of PFS vs osimertinib alone in both the high MET and ITT populations. The combination also demonstrated an encouraging clinical benefit in OS, a secondary end point, in both populations. The trial will continue to follow patients for survival outcomes.

The safety profile was consistent with the known profiles of each agent, with no new safety findings. Detailed results are slated for presentation at a forthcoming medical meeting.

“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,” said Yi-Long Wu, MD, of the Guangdong Provincial People’s Hospital and lead principal investigator of the SANOVO trial, in the press 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.”

What is the SANOVO trial design?

SANOVO is a blinded, randomized, controlled phase 3 study in patients who were previously untreated with locally advanced or metastatic NSCLC harboring activating EGFR mutations and MET overexpression in China. A total of 326 patients who were treatment-naive were randomly assigned 1:1 to receive osimertinib at 80 mg once daily plus either savolitinib or placebo at 300 mg or 200 mg twice daily, dosed based on body weight.

The primary end point was investigator-assessed PFS. Secondary end points included PFS by independent review committee assessment, OS, objective response rate, duration of response, disease control rate, time to response, and safety.

What are savolitinib and osimertinib?

Savolitinib is an oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI) that blocks atypical activation of the MET pathway resulting from mutations, gene amplification, or protein overexpression. Osimertinib is a third-generation, irreversible EGFR-TKI. Because co-occurring MET overexpression can compromise the durability of EGFR-TKI monotherapy, the combination is designed to target both pathways upfront and potentially delay osimertinib resistance driven by MET overexpression.

What is the combination’s regulatory and trial history?

Savolitinib plus osimertinib is approved in China for patients with locally advanced or metastatic EGFR-mutant NSCLC with MET amplification after disease progression on EGFR-TKI therapy, based on the phase 3 SACHI trial (NCT05015608).² Previously, the combination also demonstrated statistically significant and clinically meaningful improvements in both PFS and OS in the global phase 3 SAFFRON trial (NCT05261399) in EGFR-mutant NSCLC with MET overexpression or amplification after progression on osimertinib in August 2026.³

“We are thrilled by the positive results from SANOVO, which validate our strategy of addressing MET-driven disease across multiple stages of lung cancer. Building on the strong foundations of our phase 3 SAFFRON global study and SACHI study in China in pre-treated patients, SANOVO data further validate the therapeutic strength and versatility of the [savolitinib] and [osimertinib] combination in first-line patients,” Weiguo Su, PhD, chief executive officer and chief scientific officer of HUTCHMED, concluded.¹

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. HUTCHMED (China) Limited. August 31, 2026. Accessed September 1, 2026. https://tinyurl.com/ahwcumcn
2. HUTCHMED announces China approval for ORPATHYS® in combination with TAGRISSO® for the treatment of lung cancer patients with MET amplification after progression on first-line EGFR inhibitor therapy. News release. HUTCHMED (China) Limited. June 30, 2025. Accessed September 1, 2026. https://tinyurl.com/bdr2a6jt
3. HUTCHMED announces Orpathys plus Tagrisso demonstrated statistically significant and clinically meaningful improvements in progression-free and overall survival in MET-driven EGFR-mutated lung cancer after progression on Tagrisso (SAFFRON). News release. HUTCHMED (China) Limited. August 16, 2026. Accessed September 1, 2026. https://tinyurl.com/mr2b5ufw