A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC 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.

Inclusion criteria

• Male or female, at least ≥ 18 years.
• NSCLC, of non-squamous histology.
• Stage IA2 or IA3 disease, based on TNM8 classification.
• Complete surgical resection (R0) of the primary NSCLC by lobectomy, bilobectomy, segmentectomy or sleeve resection.
• 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.
• World Health Organization performance status of 0 or 1.
• Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.
• A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test.
• Minimum life expectancy of > 6 months.
• 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

• Mixed small cell and non-small cell cancer history.
• Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy or only wedge resection.
• 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.
• 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.
• 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.
• History of interstitial lung disease.
• Inadequate bone marrow reserve or organ function.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.
• Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs).
• Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.
• Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.