HUTCHMED (China) announced that AstraZeneca has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for Orpathys (savolitinib) in combination with Tagrisso (osimertinib) for patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) whose tumours have MET overexpression or amplification and whose disease has progressed following treatment with an Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI).

The NDA is supported by results from the global Phase 3 SAFFRON trial, which evaluated the combination against doublet platinum-based chemotherapy in patients whose disease progressed following Tagrisso treatment. The trial demonstrated statistically significant and clinically meaningful improvements in both Progression-Free Survival (PFS) and Overall Survival (OS). The safety profile was consistent with the known profiles of the individual medicines, with no new safety concerns reported.

MET overexpression or amplification is a recognised mechanism of resistance to third-generation EGFR-TKI treatment. MET-driven progression in EGFR-mutated NSCLC is associated with poor outcomes, creating a need for additional treatment options for patients whose disease progresses following EGFR-TKI therapy.

SAFFRON was a randomised, open-label, multicentre Phase III trial involving 338 patients with EGFR-mutated, locally advanced or metastatic NSCLC with MET overexpression or amplification. Patients were treated across 230 centres in 29 countries. The trial evaluated Orpathys at 300 mg twice daily in combination with Tagrisso at 80 mg once daily, compared with doublet platinum-based chemotherapy. PFS was the primary endpoint, with OS among the key secondary endpoints.

Orpathys is an oral, selective MET Tyrosine Kinase Inhibitor (TKI) that targets abnormal activation of the MET pathway resulting from gene amplification, protein overexpression or certain mutations. The medicine is jointly developed by AstraZeneca and HUTCHMED and is commercialised by AstraZeneca.

Orpathys is approved in China for adults with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations. The combination of Orpathys and Tagrisso is also approved in China for patients with EGFR mutation-positive, non-squamous NSCLC with MET amplification following disease progression on EGFR-TKI therapy, based on the Phase 3 SACHI trial. The combination has also received temporary authorisation in Switzerland for a similar patient population based on Phase 2 SAVANNAH data.

Tagrisso is a third-generation, irreversible EGFR-TKI approved in more than 120 countries, including the US, European Union, China and Japan, for multiple indications in EGFR-mutated NSCLC.

Lung cancer remains a major cause of cancer mortality globally, with NSCLC accounting for approximately 80–85 percent of lung cancer cases. Around 75% of NSCLC cases are diagnosed at an advanced stage. MET overexpression or amplification can contribute to tumour growth and disease progression, particularly following treatment with third-generation EGFR-TKIs.