A Phase III, Randomised, Open-Label Study 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 Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib.
Primary 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 Objectives:
- To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of OS in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
- 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 by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
- To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of OS in participants with EGFR mutated, MET-overexpressed by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
- To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of ORR, DoR, DCR, TDT or death, and tumour shrinkage in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
- To assess participant-reported pulmonary core symptoms of NSCLC in participants treated with savolitinib in combination with osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
- To evaluate the PK of savolitinib.
PEMETREXED
CARBOPLATIN
Osimertinib
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Missak Haigentz MD
- Principal Investigator
- RWJBarnabas Health
- Cooperman Barnabas, Livingston
- Jersey City Medical Center, Jersey City
- Newark Beth Israel Medical Center
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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.