Tagrisso plus Orpathys significantly improved progression-free survival in first-line EGFR-mutated NSCLC with MET overexpression in SANOVO.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca and HUTCHMED have reported positive high-level results from the Phase III SANOVO trial (NCT05009836), showing that Tagrisso (osimertinib) plus Orpathys (savolitinib) achieved a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) compared with Tagrisso alone in treatment-naïve patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) and MET overexpression. The PFS benefit was demonstrated in both patients with high MET expression (IHC 3+) and the broader intention-to-treat (ITT) population, which included patients with MET overexpression at IHC 2+ or IHC 3+.
A Dual-Pathway Approach in First-Line Treatment
EGFR-mutated NSCLC can respond to EGFR tyrosine kinase inhibitors (TKIs) such as Tagrisso, while MET overexpression or amplification can contribute to tumour growth and metastatic progression. The SANOVO trial evaluated whether targeting both pathways upfront with an all-oral combination could improve outcomes in treatment-naïve patients with EGFR-mutated NSCLC and MET overexpression.
SANOVO was a blinded, randomized, controlled Phase III trial conducted in China by HUTCHMED. It enrolled 326 treatment-naïve patients with locally advanced or metastatic NSCLC harbouring EGFR mutations, specifically exon 19 deletion or L858R, alongside MET overexpression. Patients were randomized 1:1 to receive Tagrisso 80 mg once daily plus either Orpathys or placebo at 300 mg or 200 mg twice daily, with dosing based on body weight. The primary endpoint was investigator-assessed PFS. Other endpoints included independently reviewed PFS, overall survival (OS), objective response rate, duration of response, disease control rate, time to response, and safety.
SANOVO Builds on Earlier Clinical Evidence
The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful PFS improvement with Tagrisso plus Orpathys versus Tagrisso alone in both the high MET expression population (IHC 3+) and the broader ITT population (IHC 2+ and IHC 3+). The combination also demonstrated very encouraging clinical benefit in OS in both populations. OS is a secondary endpoint, and the trial will continue to follow patients for further follow-up.
The findings build on evidence from the same all-oral combination in patients whose disease has progressed following EGFR-TKI treatment. Tagrisso plus Orpathys is approved in China for patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification after disease progression on EGFR-TKI therapy, based on the Phase III SACHI trial (NCT05015608).
More recently, the global Phase III SAFFRON trial (NCT05261399) reported statistically significant and clinically meaningful improvements in both PFS and OS with Tagrisso plus Orpathys in EGFRm NSCLC with MET overexpression or amplification following disease progression on Tagrisso.
Safety
The safety profile of Tagrisso plus Orpathys in the SANOVO trial was consistent with the known profiles of the individual medicines, with no new safety findings reported.
Executive Perspective
Professor Yi-Long Wu of Guangdong Provincial People’s Hospital and the trial’s leading principal investigator said the SANOVO results demonstrate the potential of addressing both EGFR and MET pathways upfront in patients with EGFR-mutated NSCLC and MET overexpression.
Leora Horn, Senior Vice President of Late Development, Oncology R&D at AstraZeneca, said the findings add to the growing evidence supporting the combination of Orpathys with Tagrisso to address MET-driven resistance and improve outcomes in patients with EGFR-mutated lung cancer.
Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said the SANOVO findings further validate the therapeutic potential of the Orpathys and Tagrisso combination across multiple stages of lung cancer and build on the results from the SAFFRON and SACHI trials.
Regulatory Path
The SANOVO data will be presented at a forthcoming medical meeting and shared with regulatory authorities. HUTCHMED said it looks forward to sharing the findings with regulators to support bringing the all-oral combination into the first-line setting in China.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.