About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.2 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have EGFR-mutated (“EGFRm”) NSCLC.3,4,5,6
MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of acquired resistance to EGFR TKI for metastatic EGFRm NSCLC.7,8
About ORPATHYS®
ORPATHYS® (savolitinib) is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.
ORPATHYS® is approved in China and is marketed by AstraZeneca for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines.
About TAGRISSO®
TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO® as a treatment for patients across multiple stages of EGFRm NSCLC.
There is an extensive body of evidence supporting the use of TAGRISSO® as standard of care in EGFRm NSCLC. TAGRISSO® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.
About ORPATHYS® and TAGRISSO® Combination Development in EGFR-mutated NSCLC
Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO® is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with ORPATHYS® in combination with TAGRISSO® has been studied extensively in these patients in the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results led to the initiation of several Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836).
This combination represents a promising chemotherapy-free oral treatment strategy to address mechanisms of resistance in this advanced setting. Positive data from the SACHI randomized Phase III trial led to the filing of a second NDA in China. Strong data from the SAVANNAH single-arm Phase II study was recently presented at the European Lung Cancer Congress (ELCC) in March 2025 demonstrated high, clinically meaningful and durable objective response rate (ORR), with consistent safety results. The SAFFRON randomized Phase III trial is progressing. Following AstraZeneca’s consultation with the US Food and Drug Administration (“FDA”), we look forward to completing the SAFFRON trial as soon as possible to support potential US and other global registration filings.
SACHI: The SACHI China Phase III trial met the primary endpoint of PFS during its interim analysis towards the end of 2024 and a NDA was accepted and granted Breakthrough Therapy Designation and Priority Review status in China in December 2024. SACHI evaluated the combination of ORPATHYS® and TAGRISSO® for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC after progression on EGFR TKI compared to platinum-based doublet chemotherapy. Results were presented at the ASCO Annual Meeting in June 2025.