Tagrisso Plus Orpathys Improves PFS in First-Line Lung Cancer

AstraZeneca (AZN ) said on September 1, 2026, that the SANOVO Phase III trial met its primary endpoint, with Tagrisso (osimertinib) plus Orpathys (savolitinib) demonstrating a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) versus Tagrisso alone in treatment-naïve patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) and MET overexpression. According to the company’s announcement, the PFS benefit was demonstrated both in patients with high MET expression (IHC 3+) and in the trial’s intention-to-treat population (IHC 2+ and IHC 3+).

The company said the combination also showed very encouraging clinical benefit in overall survival, a secondary endpoint, in both patient populations, and that the trial will continue to follow up on those results. The safety profile of Tagrisso plus Orpathys was consistent with the known profiles of each medicine, with no new safety findings. The data will be presented at a forthcoming medical meeting and shared with regulatory authorities.

Professor Yi-Long Wu of Guangdong Provincial People’s Hospital, the leading principal investigator of the trial, said co-occurring MET overexpression in treatment-naïve EGFR-mutated NSCLC often compromises the long-term durability of EGFR-TKI monotherapy. “By combining Orpathys with Tagrisso, we have observed a clear clinical benefit that could reshape primary treatment strategy for this distinct patient population,” Wu said.

Leora Horn, Senior Vice President, Late Development, Oncology R&D at AstraZeneca, said the SANOVO data build on the body of evidence for adding Orpathys to backbone Tagrisso to intercept MET-driven resistance, delay progression and improve outcomes. Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “We are thrilled by the positive results from SANOVO, which validate our strategy of addressing MET-driven disease across multiple stages of lung cancer.” Su said the partners look forward to sharing the data with regulatory authorities to bring the all-oral combination to the first-line setting in China.

SANOVO Trial Design

SANOVO is a blinded, randomized, controlled Phase III trial conducted by HUTCHMED in China in previously untreated patients with locally advanced or metastatic NSCLC with activating EGFR mutations and MET overexpression. A total of 326 treatment-naïve patients whose tumours harboured EGFR mutations (exon 19 deletion or L858R) and MET overexpression were randomized in a 1:1 ratio to receive Tagrisso 80mg once daily plus either Orpathys or placebo at 300mg or 200mg twice daily, with the dose based on body weight. The primary endpoint of the trial is PFS as assessed by investigators. Other endpoints include PFS assessed by an independent review committee, overall survival, objective response rate, duration of response, disease control rate, time to response, and safety. Tagrisso monotherapy is a standard-of-care treatment option for these patients.

Prior Approvals and Earlier Phase III Data

The Tagrisso plus Orpathys combination is already approved in China for patients with locally advanced or metastatic EGFRm NSCLC with MET amplification after disease progression on EGFR-TKI therapy, based on the SACHI Phase III trial. On August 17, 2026, AstraZeneca reported positive high-level results from the SAFFRON global Phase III trial, in which the combination demonstrated a statistically significant and clinically meaningful improvement in both PFS and overall survival versus doublet platinum-based chemotherapy in patients with EGFRm NSCLC with high levels of MET overexpression or amplification after progression on Tagrisso. SAFFRON enrolled 338 patients across 230 centres in 29 countries. The combination also holds a temporary authorisation in Switzerland for patients with locally advanced or metastatic EGFRm NSCLC and high levels of MET overexpression or amplification who progressed on prior treatment with Tagrisso, based on results from the global SAVANNAH Phase II trial.

Orpathys is an oral, potent and highly selective MET tyrosine kinase inhibitor that blocks atypical activation of the MET receptor pathway occurring because of mutations, gene amplification or protein overexpression. It is approved in China as a monotherapy for adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China, and it also holds a conditional approval in China for patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with MET amplification who have failed at least two prior systemic treatments. Orpathys is being jointly developed by AstraZeneca and HUTCHMED and is commercialised by AstraZeneca.

Tagrisso is a third-generation, irreversible EGFR-TKI with clinical activity in NSCLC, including the treatment of central nervous system metastases. AstraZeneca said the medicine has been used to treat more than one million patients across its indications worldwide. It is approved as monotherapy in more than 120 countries, including the US, EU, China and Japan, with indications covering first-line treatment of locally advanced or metastatic EGFRm NSCLC, EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC, and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. Tagrisso is also approved in combination with chemotherapy in more than 80 countries for the first-line treatment of locally advanced or metastatic EGFRm NSCLC.

Lung cancer is the leading cause of cancer death globally, accounting for almost one in four (23%) cancer deaths, according to figures cited in the announcement. NSCLC accounts for 80-85% of lung cancer diagnoses, and approximately 75% of NSCLC patients are diagnosed with advanced disease. About 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFR-mutated disease. MET is a tyrosine kinase receptor with an essential role in normal cell development, and MET overexpression or amplification can lead to tumour growth and the metastatic progression of cancer cells.