AZN Tagrisso + Orpathys Hits SANOVO PFS in MET-High NSCLC

AstraZeneca’s Tagrisso (osimertinib) plus Orpathys (savolitinib) beat Tagrisso alone on progression-free survival (PFS) in the SANOVO Phase 3 trial, a 326-patient study partner HUTCHMED (HCM) ran entirely in China. The readout covers treatment-naive patients whose EGFR-mutant non-small cell lung cancer (NSCLC) also carries MET overexpression, a trait that shortens how long EGFR inhibitors alone keep tumors in check.

The combination met its primary endpoint with a statistically significant and, in the companies’ words, “highly clinically meaningful” PFS improvement in both the high-MET group (IHC 3+) and the wider intent-to-treat population (IHC 2+ and 3+). Overall survival, a secondary endpoint, trended favorably but is still maturing. AstraZeneca and HUTCHMED withheld the actual PFS figures, saying full data will come at a future medical meeting.

Savolitinib is an oral MET tyrosine-kinase inhibitor, and osimertinib is the third-generation EGFR inhibitor that anchors most EGFR-mutant lung cancer care. MET overexpression helps tumors sidestep EGFR blockade, so attacking both growth signals at once is the logic behind the all-oral pairing.

In the MET inhibitor class, Orpathys competes with Novartis’s capmatinib (Tabrecta) and Merck KGaA’s tepotinib (Tepmetko), both cleared for MET exon 14 skipping NSCLC. The SANOVO result is specific to the Tagrisso pairing, where savolitinib’s selectivity has let AstraZeneca and HUTCHMED run a series of trials across lines of therapy. For HUTCHMED, which co-developed savolitinib and shares economics with AstraZeneca, SANOVO extends a royalty stream already underpinned by SACHI and SAFFRON.

AZN closed at $162.47 on September 1. For a mega-cap drugmaker, a China readout rarely moves the stock, and this one is no exception.

The honest framing is that this is a China registration signal, not a near-term US catalyst. Both drugs are already FDA-approved, and the combination is already cleared in China for MET-amplified NSCLC after progression on an EGFR inhibitor, based on the SACHI trial. SANOVO pushes the pairing into the first line in China, where HUTCHMED will file with regulators. The US path is separate: AstraZeneca’s global SAFFRON trial tests the same combo in a later-line MET-driven setting, not first-line.

The real question is whether MET overexpression becomes a routine upfront biomarker. If it does, the addressable population for the all-oral combo widens well beyond the smaller MET-amplification group. Roughly 30-40% of Asian NSCLC patients carry EGFR mutations, and MET overexpression or amplification drives resistance in about a third who progress on a third-generation EGFR inhibitor. In the same EGFR lung cancer field, Cullinan’s zipalertinib awaits an FDA decision for exon 20 insertion mutations.

What to watch: the full PFS and safety data at the medical meeting, plus HUTCHMED’s China submission. Separately, AstraZeneca and Daiichi Sankyo announced EU approval of Enhertu plus pertuzumab for first-line HER2-positive metastatic breast cancer.