Carcinoma, Non-Small-Cell Lung
Conditions
Interventions
Participants will be randomised in a ratio of 1:1 to receive oral treatment with 300 mg
savolitinib BID plus 80 mg osimertinib QD or platinum-based doublet chemotherapy
(cisplatin/carboplatin plus pem
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
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 or more 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
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 with the exception of alopecia, haemoglobin 9.0 g/dL or more, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| "Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. [ Time Frame: Approximately 55 months post first subject randomized ] Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause." | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Korea, Malaysia, Philippines, Poland, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, UK, USA, Vietnam
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed