Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment

Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib.

Inclusion Criteria: * Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses. * Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted. * Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy. * Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M. * Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy. * Mandatory provision of FFPE tumour tissue. * MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment. * Measurable disease as defined by RECIST 1.1. * Adequate haematological, liver, renal and cardiac functions, and coagulation parameters. * ECOG performance status of 0 or 1. Exclusion Criteria: * 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 and prior platinum-therapy related Grade 2 neuropathies with the exception of alopecia and haemoglobin ≥ 9.0 g/dL. * 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.