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

Eligibility 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.
• * 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.