Non-Small Cell Lung Cancer
Conditions
Keywords
Osimertinib, Tagrisso, NSCLC, Non-small Cell Lung Cancer, Resectable, EGFRm Positive, Adjuvant, Stage IA2-IA3
Brief summary
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.
Detailed description
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.
Interventions
DRUGOsimertinib
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.
DRUGPlacebo
Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, at least ≥ 18 years. 2. NSCLC, of non-squamous histology. 3. Stage IA2 or IA3 disease, based on TNM8 classification. 4. Complete surgical resection (R0) of the primary NSCLC by lobectomy, bilobectomy, segmentectomy or sleeve resection. 5. Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants. 6. World Health Organization performance status of 0 or 1. 7. Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation. 8. A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test. 9. Minimum life expectancy of \> 6 months. 10. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception.
Exclusion criteria
1. Mixed small cell and non-small cell cancer history. 2. Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy or only wedge resection. 3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including HCV and HIV or active uncontrolled HBV infection. 4. History of another primary malignancy, including any known or suspected synchronous primary lung cancer except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence. 5. Any of the following cardiac criteria: * Mean resting QTcF interval \> 470 ms, obtained from triplicate ECGs performed at screening. * Any abnormalities in rhythm, conduction, or morphology of resting ECG, * Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events. 6. History of interstitial lung disease. 7. Inadequate bone marrow reserve or organ function. 8. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention. 9. Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs). 10. Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention. 11. Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) in high-risk stratum | From date of randomisation up to approximately 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) in overall population | From date of randomisation up to approximately 10 years | 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. |
| Overall Survival (OS) in high-risk stratum and the overall population | From date of randomization up to approximately 10 years | OS is defined as the time from the date of randomisation until death due to any cause. |
| PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population | From date of randomisation up to approximately 10 years | Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose. |
| Impact of osimertinib versus placebo on physical functioning | From date of randomisation up to approximately 10 years | 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 |
| Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population | From date of randomisation up to approximately 10 years | 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. |
| Safety and tolerability in overall population | From date of randomisation up to approximately 10 years | AEs graded by CTCAE version 5.0 |
Countries
Argentina, Brazil, Canada, China, Germany, Italy, Japan, Malaysia, Poland, Romania, Russia, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
PRINCIPAL_INVESTIGATORJonathan Goldman, MD
University of California, Los Angeles
PRINCIPAL_INVESTIGATORYasuhiro Tsutani, MD, PhD
Kindai University Facility of Medicine
PRINCIPAL_INVESTIGATORJie He, MD, PhD
The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)
Outcome results
None listed