Stage IA2-IA3 non-small cell lung carcinoma, with EGFR mutation type (Ex19del, L858R), following complete tumour resection. MedDRA version: 21.1 Level: PT Classification code 10029517 Term: Non-small cell lung cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tagrisso
Product Name: Osimertinib 40 mg
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: osimertinib
CAS Number: 1421373-66-1
Current Sponsor code: AZD92
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
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, 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). 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. 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 190 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 190
Exclusion criteria
Exclusion criteria: 1. Mixed small cell and non-small cell cancer history. 2. Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy, bilobectomy or only wedge resection. 3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and HIV. 4. History of another primary malignancy 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 QTc 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 QTc 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 |
|---|---|
| Main Objective: To assess the efficacy of osimertinib compared to placebo as measured by disease-free survival in participants in the high-risk statum.;Secondary Objective: 1. To demonstrate the effectiveness of osimertinib versus placebo by assessment of disease-free survival (DFS) in the overall population. 2. To demonstrate the effectiveness of osimertinib versus placebo by assessment of overall survival (OS) in participants in both the high-risk stratum and the overall population. 3. To assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and overall population. 4. To assess the effectiveness of osimertinib versus placebo by assessment of central nervous system disease free survival (DFS) in both the high-risk stratum and the overall population. 5. To characterise the pharmacokinetics of osimertinib and its metabolites (AZ13575104 [AZ5104]) in the overall population. 6. To assess the safety and tolerability profile of osimertinib versus placebo in the overall population.;Primary end point(s): Disease free survival (DFS) in the high-risk stratum by investigators' assessment.;Timepoint(s) of evaluation of this end point: From randomization until recurrence or death (by any cause in the absence of recurrence). Initial analysis in 2027. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease free survival (DFS) in the overall population by investigator's assessment. - Disease free survival (DFS) in both the high-risk stratum and overall population. - Overall survival (OS) in participants in both the high-risk stratum and overall population. - Impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and overall population. - Effectiveness of osimertinib versus placebo by assessment of central nervous system disease free survival (DFS) in both the high-risk stratum and the overall population. - Characterise the pharmacokinetics of osimertinib and its metabolites (AZ13575104 [AZ5104]) in the overall population. - Safety and tolerability profile of osimertinib versus placebo in the overall population.;Timepoint(s) of evaluation of this end point: Throughout the trial. | — |
Countries
Argentina, Austria, Brazil, Canada, China, Germany, Italy, Japan, Korea, Republic of, Malaysia, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed