SAFFRON: This study is investigating how safe and effective combination targeted therapy is compared to platinum-based doublet chemotherapy in people with EGFR-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic non-small lung cancer who have progressed on treatment with osimertinibA Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib (SAFFRON).

Exclusion

• Predominant squamous NSCLC, and small cell lung cancer.
• Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.
• Prior or current treatment with savolitinib or another MET inhibitors.
• Spinal cord compression or brain metastases, unless asymptomatic and are stable.
• History or active leptomeningeal carcinomatosis.
• Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 with the exception of alopecia, haemoglobin ≥ 9.0 g/dL, and Grade 2 prior platinum-therapy related neuropathy.
• Active/unstable cardiac diseases currently or within the last 6 months, clinically significant ECG abnormalities, and/or factors/medications that may affect QTc intervals.
• History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement.
• Known serious active infection including, but not limited to, tuberculosis, or HIV, HBV or HCV or gastrointestinal disease.
• Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of study intervention.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
• Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.