HUTCHMED and AstraZeneca Report Positive Phase III SAFFRON Results in EGFR-Mutated Lung Cancer

HONG KONG, SHANGHAI AND FLORHAM PARK, N.J. — October 26, 2026

SAFFRON Demonstrates Benefits Across MET Biomarker Groups

SAFFRON was a randomized, open-label, multicenter global Phase 3 trial involving 338 patients across 230 centers in 29 countries. Participants had locally advanced or metastatic EGFRm NSCLC with high levels of MET overexpression or amplification and disease progression after first- or second-line treatment with TAGRISSO. Patients were randomized to receive ORPATHYS at 300 mg twice daily alongside TAGRISSO at 80 mg once daily, or doublet platinum-based chemotherapy. PFS was the primary endpoint, and OS was a key secondary endpoint. The full analysis set included 171 patients in the combination group and 167 in the chemotherapy group. The PFS benefit was consistent across prespecified subgroups, including patients whose tumors demonstrated MET overexpression or amplification. In the MET-overexpressed analysis set, median PFS was 8.5 months with the combination versus 5.6 months with chemotherapy, with a hazard ratio of 0.51 (95% CI, 0.37–0.71; p<0.001). The estimated 12-month PFS rate was 40%, compared with 11% in the chemotherapy group. In the MET-amplified analysis set, median PFS was approximately 7.6 months with the combination and 4.2 months with chemotherapy. The hazard ratio was 0.487 (95% CI, 0.35–0.66), and estimated 12-month PFS rates were 33% and 8%, respectively. The company noted that no formal statistical testing was conducted for the MET-amplified analysis set. The results highlight the importance of biomarker testing to identify patients whose tumors may be driven by MET-related resistance mechanisms. MET is a receptor tyrosine kinase involved in cellular growth and development; its overexpression or gene amplification can contribute to tumor progression. In some EGFR-mutated lung cancers, MET alterations emerge as a mechanism of resistance after EGFR-targeted therapy. Combining a selective MET inhibitor with continued EGFR inhibition is intended to target both signaling pathways. The SAFFRON findings support this treatment rationale, although individual outcomes may vary and treatment decisions require assessment of a patient’s tumor characteristics, prior treatment and clinical condition.

Combination Safety and Regulatory Progress

The safety profile of ORPATHYS plus TAGRISSO was described as manageable and consistent with the known safety profiles of the individual medicines, with no new safety concerns identified in the trial. Grade 3 or higher treatment-emergent adverse events from all causes occurred in 64% of patients receiving the combination and 63% receiving chemotherapy. Median total treatment exposure was 8.5 months in the combination group, more than twice the 3.5 months reported for the comparator group. The longer exposure reflects the time patients remained on treatment and should be considered when interpreting safety findings across treatment arms. The PFS and OS analyses used a data cutoff of July 6, 2026. Based on the SAFFRON results, HUTCHMED submitted an NDA to the U.S. FDA for ORPATHYS plus TAGRISSO for patients with locally advanced or metastatic NSCLC whose tumors have high levels of MET overexpression or amplification and whose disease progressed on or after EGFR-TKI therapy. Regulatory submissions in Europe and Japan are also progressing. The combination is already approved in China for patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification following progression on EGFR-TKI treatment, based on the Phase 3 SACHI trial. It also received temporary authorization in Switzerland for a related patient population based on the Phase 2 SAVANNAH study. The SAFFRON findings add global Phase 3 survival data to the clinical evidence supporting the combination in MET-driven resistance. Separately, results from the SANOVO Phase 3 trial, evaluating ORPATHYS plus TAGRISSO in treatment-naïve patients in China with EGFRm locally advanced or metastatic NSCLC and MET overexpression, were scheduled for presentation at ESMO 2026. These programs examine the combination in different treatment settings and patient populations.

HUTCHMED and AstraZeneca Advance Targeted Lung Cancer Treatment

ORPATHYS is an oral, selective MET tyrosine kinase inhibitor developed by HUTCHMED and AstraZeneca, while TAGRISSO is a third-generation EGFR TKI with established use in EGFR-mutated NSCLC. The combination is designed to inhibit MET-driven resistance while maintaining suppression of EGFR signaling. HUTCHMED and AstraZeneca are jointly developing ORPATHYS, with AstraZeneca responsible for commercialization. The companies are pursuing the approach as a biomarker-directed treatment option for patients whose cancer progresses after EGFR-targeted therapy. The SAFFRON study is significant because it evaluated both progression-free and overall survival against platinum-based chemotherapy in a global Phase 3 setting. Nevertheless, regulatory status differs by jurisdiction, and the combination’s approval in China or temporary authorization in Switzerland should not be interpreted as approval in every market. HUTCHMED is a commercial-stage biopharmaceutical company focused on discovering, developing and commercializing targeted therapies and immunotherapies for cancer and immunological diseases. Its oncology portfolio includes medicines and investigational programs directed at molecular drivers of disease. AstraZeneca continues to develop treatments for lung cancer, including therapies targeting EGFR and resistance pathways. The SAFFRON data support continued evaluation of biomarker-guided treatment after EGFR-TKI progression and reinforce the role of MET testing in treatment selection. The next regulatory milestones will be important in determining the combination’s availability across additional markets. Further clinical practice will depend on regulatory decisions, patient eligibility, local treatment guidelines and the evolving evidence base.

Source:HUTCHMED,Press release