A late stage clinical trial to investigate the efficacy and safety of AZD9291 versus Placebo in patients with stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy

INTERVENTION: Product Name: AZD9291 80 mg film‐coated tablet Product Code: AZD9291 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Not yet assigned CAS Number: 1421373‐66‐1 Current Sponsor code: AZD9291 mesylate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: AZD9291 40 mg film‐coated tablet Product Code: AZD9291 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Not yet assigned CAS Number: 1421373‐66‐1 Current Sponsor code: AZD9291 mesylate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Stage IB‐IIIA non‐small cell lung carcinoma, with a centrally confirmed, common sensitising EGFR mutations (Ex19del and L858R either alone or in combination with other EGFR mutations), following complete tumour resection with or without adjuvant chemotherapy ; MedDRA version: 18.0 Level: PT Classification code 10029520 Term: Non‐small cell lung cancer stage IIIA System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 18.0 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) ; MedDRA version: 18.0 Level: PT Classification code 10029518 Term: Non‐small cell lung cancer stage II System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To assess the efficacy of AZD9291 compared to placebo as measured by disease free survival (DFS) Primary end point(s): Disease free survival (DFS) using investigator assessments Secondary Objective: 1) To further assess the efficacy of AZD9291 compared with placebo by assessment of DFS rate at 2 years, 3 years and 5 years, of OS and OS rate at 5 years; 2) To assess the effect of AZD9291 compared with placebo on health‐related quality of life (HRQoL) by assessment of patient health‐related quality of life and symptoms (HRQoL) using SF‐36 questionnaire (version 2); 3) To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) by assessment of PK exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550.; 4) To assess the safety and tolerability profile of AZD9291 compared with placebo by assessment of number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment Timepoint(s) of evaluation of this end point: At baseline and from randomization until recurrence SECONDARY OUTCOME: Secondary end point(s): 1) Assessment of Disease free survival (DFS) rate at 2 years, 3 years and 5 years; 2) Analysis of Overall Survival (OS) ; 3) Assessment of Overall Survival (OS) rate at 5 years; 4) Assessing of patient health‐related quality of life and symptoms (HRQoL) using SF‐36 questionnaire (version 2, standard) ; 5) PK exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550. ; Pharmacokinetics data from this study will be analysed using a population PK approach and may also form part of a pooled analysis with other AZD9291 studies; results from these analyses will be reported separately from the CSR; 6) Safety and tolerability endpoints assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment Timepoint(s) of evaluation of this end point: Throughout the trial INCLUSION CRITERIA: 1. Male or female, aged at least 18 years. 2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non‐squamous histology 3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care. 4. Patients must be classified post‐operatively as Stage IB, II or IIIA on the basis of pathologic criteria. 5. Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR‐TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M. 6. 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. 7. Complete recovery from surgery and standard post‐operative therapy (if applicable) at the time of randomization. 8. World Health Organization