Cambridge, UK, September 1, 2026
AstraZeneca has announced positive high-level results from the Phase III SANOVO trial, showing that Tagrisso (osimertinib) plus Orpathys (savolitinib) produced a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) compared with Tagrisso alone in previously untreated patients with EGFR-mutated (EGFRm), locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET overexpression. The findings strengthen the clinical development strategy of combining EGFR and MET pathway inhibition in patients whose tumors show both molecular characteristics. The PFS benefit was observed in both patients with high MET expression (IHC 3+) and the broader intention-to-treat population comprising patients with IHC 2+ and IHC 3+ MET expression.
SANOVO Phase III Trial Shows Significant PFS Benefit
The SANOVO Phase III trial, conducted in China by HUTCHMED, evaluated the efficacy and safety of Orpathys in combination with Tagrisso against Tagrisso alone in treatment-naïve patients with locally advanced or metastatic NSCLC carrying activating EGFR mutations and MET overexpression. A total of 326 patients with EGFR exon 19 deletion or L858R mutations were randomized in a 1:1 ratio to receive Tagrisso 80 mg once daily together with either Orpathys or placebo. The primary endpoint was investigator-assessed PFS, while secondary endpoints included overall survival (OS), objective response rate, duration of response, disease control rate and safety. AstraZeneca reported that the combination achieved the primary endpoint, with the PFS improvement considered both statistically significant and highly clinically meaningful. Encouraging clinical benefit was also observed for overall survival, although the trial will continue follow-up for OS results.
Tagrisso and Orpathys Target EGFR and MET Pathways
The scientific rationale behind the combination centers on simultaneously addressing EGFR-driven and MET-driven tumor biology. Tagrisso is a third-generation, irreversible EGFR tyrosine kinase inhibitor (EGFR-TKI) with established activity in EGFR-mutated NSCLC, including disease involving the central nervous system. Orpathys is an oral, selective MET-TKI designed to inhibit the MET receptor pathway, which can become activated through MET amplification, mutations or protein overexpression. According to AstraZeneca, MET overexpression or amplification can contribute to tumor growth and metastatic progression and may compromise the durability of EGFR-TKI treatment. By targeting both pathways from the beginning of treatment, the SANOVO findings suggest a potential strategy for addressing this distinct biomarker-defined patient population.
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Findings Build on Earlier Tagrisso-Orpathys Evidence
The SANOVO results add to previous evidence supporting the Tagrisso-Orpathys combination. The companies previously reported positive results from the global Phase III SAFFRON trial, which evaluated the combination in EGFR-mutated NSCLC with MET overexpression or amplification following disease progression on Tagrisso. In China, the Phase III SACHI trial supported approval of the combination for patients with EGFR-mutated non-squamous NSCLC and MET amplification after progression on EGFR-TKI therapy. The new SANOVO findings extend investigation of the combination into the first-line treatment setting, potentially broadening its clinical role. The safety profile of Tagrisso plus Orpathys was reported as consistent with the known profiles of the individual medicines, with no new safety findings identified in the high-level results. Detailed data are expected to be presented at a forthcoming medical meeting and shared with regulatory authorities. The companies said the findings reinforce Tagrisso as a backbone therapy across EGFR-mutated lung cancer and support further development of biomarker-directed treatment strategies. Orpathys is jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. With lung cancer remaining a major global cause of cancer mortality and EGFR mutations representing a significant subset of NSCLC, the SANOVO findings could have implications for how clinicians approach patients whose tumors demonstrate both EGFR mutations and MET overexpression. Regulatory discussions and additional clinical data will be important in determining whether the combination can move toward first-line use in this population.
Source: AstraZeneca press release
