EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Sponsors
AstraZeneca AB
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 (= 20 years of age in Japan) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 259 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of PFS in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.;Secondary Objective: In participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib, treated with savolitinib in combination with osimertinib versus platinum doublet chemotherapy: To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of: 1) OS (MET-overexpressed and/or amplified) 2) PFS (MET-overexpressed by IHC) 3) OS (MET-overexpressed by IHC) 4) ORR, DoR, DCR, TDT or death, and tumour shrinkage, (MET-overexpressed and/or amplified). 5) To assess participant-reported pulmonary core symptoms of NSCLC. 6) To evaluate the PK of savolitinib. 7) To evaluate the safety and tolerability of savolitinib in combination with osimertinib versus platinum doublet chemotherapy.;Primary end point(s): PFS as defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in participants with centrally confirmed MET IHC+ and/or MET FISH+ status (FAS). The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1 progression.;Timepoint(s) of evaluation of this end point: Approximately 55 months post first subject randomized | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) to 5) and 7) Approximately 55 months post first subject randomized. 6) 6 weeks after last patient dosed.;Secondary end point(s): 1) Overall survival defined as time from randomisation until the date of death due to any cause. 2) Progression-free survival defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in centrally confirmed MET IHC+ population of FAS (FAS-IHC+). 3) Overall survival defined as time from randomisation until the date of death due to any cause in FAS-IHC+. 4) -Objective response rate will be based on BOR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1. -Duration of response defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR, or death in the absence of disease progression. -Disease control rate defined as the proportion of participants who have BOR of a CR, PR, or stable disease, as determined by BICR per RECIST 1.1. -Time to discontinuation of treatment or death is defined as the time from date of randomisation to the earlier of the date of study intervention discontinuation (i.e., discontinuation of the last study intervention in the combination) or death. -Tumour shrinkage defined as percentage change in tumour size in accordance with RECIST 1.1. 5) -TTD in pulmonary core symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ. -TTD is defined as the time from randomisation until the date of deterioration. 6) Plasma concentrations of savolitinib and its metabolites in the PK Analysis Set. 7) Safety and tolerability will be evaluated in terms of AEs, SAEs, discontinuation rate due to AEs and deaths; clinical chemistry/haematology including LFTs; ECHOs/MUGAs, ECGs, ECOG performance status and vital signs in the Safety Analysis Set. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Viet Nam
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed