Editor's Note: This story will be updated Oct. 26 to include detailed Sanovo trial results.
AstraZeneca has offered a detailed look at the phase 3 non-small cell lung cancer data that finally position its Hutchmed-partnered Orpathys for an FDA approval more than five years after the MET inhibitor’s initial go-ahead in China.
The combination of AZ’s Tagrisso and Orpathys (savolitinib) significantly improved overall survival by 32% versus chemotherapy in patients with previously treated, EGFR-mutated NSCLC with high levels of MET alterations, according to results from the phase 3 Saffron trial shared at the European Society for Medical Oncology 2026 Congress in Madrid.
The combo extended the median length of OS by 4.9 months to 17.8 months in these patients who had all previously tried Tagrisso.
Progression-free survival was also prolonged, by 2.2 months at the median, to 7.6 months, translating into a 45% risk reduction.
Based on the Saffron results, which were also published in The New England Journal of Medicine, AZ filed for an approval with the FDA in September.
About a third of patients with EGFR-mutant NSCLC develop MET overexpression or amplification following third-generation EGFR tyrosine kinase inhibitors, AZ’s oncology R&D head, Susan Galbraith, Ph.D., told Fierce in an interview.
The Saffron readout, together with a separate positive trial for the Tagrisso-Orpathys combo in first-line MET-overexpressing tumors, “shows that this all-oral targeted regimen is really effective in this disease,” Galbraith said.
AZ partnered up with Hutchmed on savolitinib, then called volitinib, in 2011 in one of the British pharma’s very first deals with a Chinese biotech. At the time, the inhibitor of the c-Met receptor was about to enter phase 1 testing. The development time for the drug took so long partly because AZ had to narrow its focus during phase 2.
In the Saffron trial, patients’ tumors must have MET overexpression, defined by a staining intensity of 3+ for MET in at least 90% of tumor cells on immunohistochemical (IHC) analysis, or MET amplification, defined by at least 10 MET gene copies on fluorescence in situ hybridization (FISH).
AZ picked these MET cutoffs during the phase 2 Savannah study, which initially enrolled a broad population with an IHC3+ score in at least 50% of tumor cells or FISH 5+ gene amplification. But early analyses showed that patients with IHC3+ lower than 90% or below FISH10+ only had 9% objective response rate, forcing the company to pick a smaller population instead.
In Saffron, Tagrisso and Orpathys showed similar results between the MET overexpressed and amplified subgroups, improving their PFS by 49% and 52%, respectively, and OS by 26% and 45%, respectively. Among these subgroup data, only the MET-overexpressed analyses were formally tested for statistical significance.
Consistent data were also observed in Asian and non-Asian patients, with or without brain metastases, and across different EGFR mutation status and previous line of therapy.
Data from the phase 3 Sanovo trial, which pitted the Tagrisso-Orpathys combo against Tagrisso alone in treatment-naïve Chinese patients with MET-overexpressed, EGFR-mutated NSCLC, will also be presented at ESMO. AZ previously announced in September that the trial met its PFS endpoint and showed a “very encouraging clinical benefit” in OS.
On whether AZ plans to launch a global version of Sanovo in the first-line setting, Galbraith said: “We will talk to regulatory authorities about the opportunity there.”
The AZ exec then hinted at the possibility that the company might not need to duplicate the China-only Sanovo study in a full-scale global phase 3 to support its U.S. registrational strategy. EGFR mutations are more common in Asian populations.
“I think quite often when you’re looking at China-only studies, there’s a question about whether the effect size is similar if you took it into a Western patient population” Galbraith said. “The applicability, I think the Saffron data, together with the Sanovo data, really help to reassure on that point.”
AZ recently went back to China to strike another EGFR deal, acquiring FDA-approved Zegfrovy from its own spinout Dizal Pharmaceutical on the heels of positive first-line NSCLC data. The drug is currently approved to treat NSCLC with EGFR exon 20 insertion mutations, and Galbraith sees an opportunity to expand the drug’s reach to other indications, pointing to its potential in EGFR PACC mutations, as well as in earlier-stage settings.