A Study of 5 Years of Adjuvant Osimertinib in Completely Resected Epidermal Growth Factor Receptor Mutation (EGFRm) Non-small Cell Lung Carcinoma (NSCLC)

Study Overview
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Brief Summary
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To assess the efficacy and safety of osimertinib in participants with EGFRm positive stage II-IIIB NSCLC, following complete tumour resection with or without adjuvant chemotherapy.

Detailed Description
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This is a phase 2 open-label study to assess the efficacy and safety of osimertinib in participants with stage II-IIIB NSCLC with sensitising EGFR mutations. The study is designed to evaluate 5 years of adjuvant osimertinib therapy.

Official Title
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An Open-label, Single-arm, Phase II, Multinational, Multicentre Study to Assess the Efficacy and Safety of 5 Years of Osimertinib in Participants With EGFRm-positive Stage II-IIIB NSCLC, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy

Conditions
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Stage II-IIIB Non-small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: Osimertinib 80 mg/40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged at least 18 years. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology. Magnetic Resonance Imaging (MRI) or contrast computed tomography (CT) scan of the brain. Participants must be classified post-operatively as Stage II, IIIA, or IIIB on the basis of surgical pathologic criteria. Confirmation by the local laboratory that the tumour harbours one of the two common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo EGFR mutation resulting in substitution of threonine with methionine at amino acid position 790 in exon 20 of EGFR (T790M) or uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort). Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. Complete recovery from surgery and standard post-operative therapy (if applicable) at start of study intervention. World Health Organisation Performance Status of 0 to 1. Female participants must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential. Male participants must use effective barrier contraception. Exclusion Criteria: Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study drug. Participants currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior to first dose). Participants who have had only segmentectomies or wedge resections. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of study intervention. Treatment with any of the following: Pre-operative or post-operative or planned radiation therapy for the current lung cancer. Pre-operative (neo-adjuvant) platinum-based or other chemotherapy. Any prior anticancer or immunological therapy, including investigational therapy, for treatment of NSCLC other than standard platinum-based doublet post-operative adjuvant chemotherapy. Prior treatment with neoadjuvant or adjuvant EGFR tyrosine kinase inhibitor (TKI). Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib. Any of the following cardiac criteria: Mean resting corrected QT (QTc) interval > 470 msec, obtained from 3 electrocardiograms (ECGs). Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events. Heart failure, congenital long QT interval (QT) syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP). Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD. Inadequate bone marrow reserve or organ function. Women who are breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Osimertinib<br>Participants will receive osimertinib (AZD9291). | Drug: Osimertinib 80 mg/40 mg<br>* Participants will receive osimertinib (80 mg or 40 mg orally, once daily).<br>* Other names: AZD9291;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Efficacy of Osimertinib as Measured by Disease Free Survival (DFS) [Common EGFRm Cohort]. | Defined as time from date of first dose until disease recurrence, or death due to any cause in the absence of recurrence. | From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival Rate at 3, 4 and 5 Years (Uncommon EGFRm Cohort) | Defined as the proportion of participants alive and disease free at 3, 4, and 5 years. | From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years. | 
| DFS Rate at 3 and 4 Years (Common EGFRm Cohort) | Defined as the proportion of participants alive and disease free at 3, and 4 years. | From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, and 4 years. | 
| Overall Survival (OS) [Common EGFRm Cohort] | Defined as time from date of first dose until the date of death due to any cause. | From date of first dose until the date of death due to any cause, up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years. | 
| Safety and tolerability in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort) | Adverse Events (AEs) graded by CTCAE version 5.0. | From date of first dose up to approximately 5 years | 
| Recurrence events in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort) | Local/regional, or distant recurrence events assessed. | From date of first dose up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage II-IIIB Non-small Cell Lung Cancer, Adjuvant osimertinib, Adjuvant chemotherapy