This is a global study to assess the effects of osimertinib in participants with EGFRm stage IA2-IA3 non-small cell lung cancer following complete tumour resection.
This is a Phase III, double-blind, randomised, placebo-controlled, 2-arm, international study assessing the efficacy and safety of adjuvant osimertinib versus placebo in participants with stage IA2-IA3 EGFRm Non-Small Cell Lung Cancer, who have previously undergone complete tumour resection. All participants must have had a tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). Eligible participants will be randomised in a 1:1 ratio to one of the 2 intervention arms: osimertinib 80 mg or matching placebo, once daily for 3 years unless discontinuation criteria is met.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
390
The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease recurrence, unacceptable toxicity or other discontinuation criteria are met.
Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.
Disease-Free Survival (DFS) in high-risk stratum
DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first. Stratification to the high risk stratum will be based on pathologic features assessed by central pathology review during screening.
Time frame: From date of randomisation up to approximately 10 years
Disease-Free Survival (DFS) in overall population
DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.
Time frame: From date of randomisation up to approximately 10 years
Overall Survival (OS) in high-risk stratum and the overall population
OS is defined as the time from the date of randomisation until death due to any cause.
Time frame: From date of randomization up to approximately 10 years
PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population
Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose.
Time frame: From date of randomisation up to approximately 10 years
Impact of osimertinib versus placebo on physical functioning
Assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and the overall population as measured by SF-36 V2 health survey
Time frame: From date of randomisation up to approximately 10 years
Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population
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Research Site
Anchorage, Alaska, United States
Research Site
Los Angeles, California, United States
Research Site
Orange, California, United States
Research Site
Grand Junction, Colorado, United States
Research Site
Newark, Delaware, United States
Research Site
Atlanta, Georgia, United States
Research Site
Chicago, Illinois, United States
Research Site
Frederick, Maryland, United States
Research Site
Morristown, New Jersey, United States
Research Site
Flushing, New York, United States
...and 129 more locations
CNS DFS is defined as the time from randomisation to the time of a CNS lesion (as assessed by investigator) or death due to any cause, regardless of whether the participant withdraws from study intervention or receives other anti-cancer therapy.
Time frame: From date of randomisation up to approximately 10 years
Safety and tolerability in overall population
AEs graded by CTCAE version 5.0
Time frame: From date of randomisation up to approximately 10 years