AstraZeneca and HUTCHMED have reported positive Phase III results for the combination of Tagrisso (osimertinib) and Orpathys (savolitinib) in lung cancer patients.
This, with the all-oral treatment delivering a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) in previously untreated patients with EGFR-mutated lung cancer and MET overexpression.
The findings from the SANOVO trial in China strengthen the case for Tagrisso as a backbone treatment for EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), while expanding the potential role of the Tagrisso-Orpathys combination into the first-line setting.
The PFS benefit was demonstrated in both patients with high levels of MET overexpression (IHC 3+) and the broader intention-to-treat population, which included patients with IHC 2+ and IHC 3+ disease.
The combination also showed encouraging clinical benefit in overall survival (OS), a secondary endpoint, in both populations. The trial will continue to follow patients for further survival data.
Professor Yi-Long Wu of the Guangdong Provincial People's Hospital, and the leading principal investigator of the trial, said: “Co-occurring MET overexpression in treatment-naïve EGFR-mutated non-small cell lung cancer often compromises the long-term durability of EGFR-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 tumours have MET overexpression. By combining Orpathys with Tagrisso, we have observed a clear clinical benefit that could reshape primary treatment strategy for this distinct patient population.”
Leora Horn, Senior Vice President, Late Development, Oncology R&D, AstraZeneca, said: “These positive data from the SANOVO trial build on the growing body of evidence demonstrating the benefit of adding Orpathys to backbone Tagrisso to intercept MET-driven resistance, delay progression and improve outcomes for these patients. By developing novel, biomarker-directed combinations that improve upon established standards of care, AstraZeneca continues to raise the bar for patients with EGFR-mutated lung cancer.”
Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “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 III SAFFRON global study and SACHI study in China in pre-treated patients, SANOVO data further validate the therapeutic strength and versatility of the Orpathys and Tagrisso combination in first-line patients.
"We are deeply grateful to all patients and investigators who participated in the trial, and we look forward to sharing the data with regulatory authorities to bring this innovative all-oral combination to the first-line setting in China.”
The safety profile of Tagrisso plus Orpathys was consistent with the known safety profiles of the individual medicines, with no new safety findings reported.
The randomized, blinded Phase III SANOVO trial enrolled 326 previously untreated patients in China with locally advanced or metastatic NSCLC carrying activating EGFR mutations — exon 19 deletions or L858R — and MET overexpression.
Patients were randomized 1:1 to receive Tagrisso 80mg once daily plus either Orpathys or placebo. Orpathys was administered at 300mg/200mg twice daily based on body weight.
The trial’s primary endpoint is investigator-assessed PFS. Secondary endpoints include independently assessed PFS, OS, objective response rate, duration of response, disease control rate, time to response and safety.
