Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib

This study (the SAVANNAH study) will investigate the efficacy of osimertinib in combination with savolitinib in participants with epidermal growth factor receptor mutation positive (EGFRm+) and mesenchymal epithelial transition factor positive (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed following treatment with osimertinib.

Inclusion criteria: * Participants must be ≥18 years of age (≥20 years of age in Japan). All genders are permitted. * Histologically or cytologically confirmed locally advanced or metastatic EGFRm+ NSCLC harbouring an EGFR mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity and permitted in the osimertinib national label (such as either exon 19 deletion and/or L858R) which is not amenable to curative therapy. * Documented radiologic disease progression on first-line (1L) osimertinib. * MET amplification and/or overexpression (FISH10+ and/or IHC90+) as determined by FISH (central) and IHC (central) testing on tumour sample collected following progression on 1L osimertinib treatment. * Available tumour sample for central MET FISH and IHC analysis or willingness to collect additional sample for central testing which fulfils the following requirements: Obtained following progression on previous osimertinib therapy; obtained within 2 years of submission for MET analysis; sufficient tissue to meet the minimum tissue requirement defined in the current Laboratory Manual. * At least 1 lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used as long as baseline tumour assessment scans are done at least 14 days after the screening tumour sample collection is performed. * Prior lines of therapy in locally advanced/metastatic setting: Only prior 1L osimertinib treatment in metastatic setting is permitted. * Adequate haematological function defined as: * Absolute neutrophil count ≥1500/μL * Haemoglobin ≥9 g/dL (no transfusion in the past 2 weeks) * Platelets ≥100,000/μL (no transfusion in the past 10 days) * Adequate liver function * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) with total bilirubin (TBL) ≤ ULN OR * TBL \> ULN to ≤1.5x ULN with ALT and AST ≤ ULN * Adequate renal function - defined as a serum creatinine \1.5 times ULN. * Adequate coagulation parameters: INR \450 msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value. Any factors that may increase the risk of QTcF prolongation or risk of arrhythmic events such as heart failure, chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs, eg, complete left bundle branch block, third degree heart block, second degree heart block, P-R interval \>250 msec. Acute coronary syndrome * Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. * Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days * Evidence of severe or uncontrolled systemic diseases, including renal transplant, active bleeding diatheses or uncontrolled hypertension, which in the investigator's opinion makes it undesirable for the participant to participate * Active hepatitis B or C or known serious active infection e.g. tuberculosis or human immunodeficiency virus. Viral testing is not required for assessment of eligibility for the study. * Known serious active infection including, but not limited to, tuberculosis, or human immunodeficiency virus (positive human immunodeficiency virus 1/2 antibodies). * Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years. Participants with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All participants with previously treated in situ carcinoma (ie, non-invasive) are eligible, as are participants with history of non-melanoma skin cancer. * Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study treatment. * Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. * History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal liver function tests (LFTs), * Prior or current treatment with a 3rd generation EGFR-TKI other than osimertinib * Prior or current treatment with savolitinib or another MET inhibitor (eg, foretinib, crizotinib, cabozantinib, onartuzumab, capmatinib). * Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days prior to the first dose of study treatment with the exception of monotherapy osimertinib which may continue uninterrupted during screening. * Participants currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4, strong inhibitors of CYP1A2 within 3 weeks of the first dose of study treatment (including St John's Wort). * Participation in another clinical study with a cytotoxic, investigational product (IP), or other anticancer drug for the treatment of advanced NSCLC if received IP from that study within 14 days of the first dose of study treatment. * Known hypersensitivity to the active or inactive excipients of osimertinib or savolitinib or drugs with a similar chemical structure or class.