Tagrisso Plus Orpathys Improves Progression-Free Survival in Lung Cancer

Patients with previously untreated EGFR-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) who also had MET overexpression experienced a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) when treated with Tagrisso (osimertinib) plus Orpathys (savolitinib) compared with Tagrisso alone, according to results from the phase 3 SANOVO trial in China announced by AstraZeneca and HUTCHMED.

The trial was designed to test whether treating the EGFR and MET pathways together, from the start of treatment, could help patients whose tumors carry MET overexpression alongside their EGFR mutation, a combination that can limit how long EGFR-targeted therapy alone stays effective.

What Data Support the Findings?

The PFS improvement with Tagrisso plus Orpathys was seen in both the high MET group, defined as IHC 3+, and the intention-to-treat (ITT) population, which included patients with IHC 2+ and IHC 3+ MET expression. In both of these patient groups, the combination also showed encouraging results for overall survival (OS), a secondary endpoint of the trial. Investigators said this OS data is still developing and that the trial will continue following patients to gather more information on survival outcomes.

Yi-Long Wu, of Guangdong Provincial People's Hospital and the trial's leading principal investigator, said co-occurring MET overexpression in treatment-naive EGFR-mutated NSCLC often compromises how long EGFR-TKI therapy alone remains durable. He said the SANOVO findings show that addressing both pathways upfront with an all-oral, biomarker-directed regimen offers "a powerful new approach" for patients whose tumors have MET overexpression, and that the clinical benefit observed could reshape how this specific patient population is treated first.

Leora Horn, senior vice president of late development, oncology research and development, at AstraZeneca, said the SANOVO results build on a growing body of evidence showing that adding Orpathys to Tagrisso can help intercept MET-driven resistance, delay disease progression and improve outcomes for these patients.

Weiguo Su, chief executive officer and chief scientific officer of HUTCHMED, said the results validate the companies' strategy of addressing MET-driven disease across multiple stages of lung cancer, building on the earlier phase 3 SAFFRON global study and SACHI study in China, both of which enrolled patients who had already received prior treatment.

What Are the Details of the SANOVO Trial?

SANOVO is a blinded, randomized, controlled phase 3 trial conducted by HUTCHMED in China. It enrolled 326 patients with locally advanced or metastatic NSCLC who had not yet received treatment, whose tumors carried an EGFR mutation, either exon 19 deletion or L858R, along with MET overexpression.

Patients were randomly assigned in a 1:1 ratio to receive Tagrisso at 80 mg once daily plus either Orpathys or a placebo. Orpathys or placebo was dosed at 300/200 mg twice daily, based on each patient's body weight. Tagrisso alone represents a standard-of-care treatment option for this patient population.

The trial's primary endpoint is PFS as assessed by investigators. Additional endpoints include PFS as assessed by an independent review committee, OS, objective response rate, duration of response, disease control rate, time to response and safety.

What Side Effects Were Reported?

The safety profile of Tagrisso plus Orpathys in the SANOVO trial was consistent with the known safety profiles of each medicine individually, and no new side effects were identified. Full safety data from the trial will be presented at an upcoming medical meeting and shared with regulatory authorities.

Tagrisso plus Orpathys is already approved in China for patients with locally advanced or metastatic EGFRm NSCLC with MET amplification whose disease progressed after treatment with an EGFR-TKI, based on results from the phase 3 SACHI trial. The combination also recently reported positive results in the global phase 3 SAFFRON trial, which evaluated patients with EGFRm NSCLC and MET overexpression or amplification whose disease progressed after Tagrisso treatment, showing a statistically significant and clinically meaningful improvement in both PFS and OS. Orpathys is being jointly developed by AstraZeneca and HUTCHMED and is commercialized by AstraZeneca.

References

1. "Tagrisso plus Orpathys demonstrated statistically significant and highly clinically meaningful improvement in progression-free survival in 1st-line MET-overexpressing EGFR-mutated lung cancer" News Release. AstraZeneca, September 1, 2026.

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