Primary Hypothesis The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with Central Nervous System (CNS) metastasis Secondary Hypothesis The safety profile of AZD3759 is comparable to EGFR TKI first-line treatment in patients with advanced NSCLC with CNS metastasis.
Name: AZD3759
Name: Erlotinib
Name: Gefitinib
Description: To assess if first line treatment with AZD3759 results in significant PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using RECIST 1.1.
Measure: PFS assessed by Blinded Independent Central Radiological Time: 36 monthsDescription: Investigator assessment of PFS using RECIST 1.1
Measure: PFS assess by investigator Time: 36 monthsDescription: Intracranial PFS (iPFS) assessed by investigator using RECIST 1.1
Measure: Intracranial PFS (iPFS) assessed by investigator Time: 36 monthsDescription: Intracranial PFS (iPFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1
Measure: Intracranial PFS (iPFS) assessed by BICR Time: 36 monthsDescription: Extracranial PFS (ePFS) assessed by investigator using RECIST 1.1
Measure: Extracranial PFS (ePFS) assessed by investigator Time: 36 monthsDescription: Extracranial PFS (ePFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1
Measure: Extracranial PFS (ePFS) assessed by BICR Time: 36 monthsDescription: Objective Response Rate (ORR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
Measure: Objective Response Rate (ORR) assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: Disease Control Rate (DCR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
Measure: Disease Control Rate (DCR) assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: Duration of Response (DoR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
Measure: Duration of Response (DoR) assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: Overall ORR assessed by investigator using RECIST 1.1
Measure: Overall ORR assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: Overall DCR assessed by investigator using RECIST 1.1
Measure: Overall DCR assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: Overall DoR assessed by investigator using RECIST 1.1
Measure: Overall DoR assessed by investigator using RECIST 1.1 Time: 36 monthsDescription: ORR for Intracranial lesions assessed by investigator using RANO-BM
Measure: ORR for Intracranial lesions assessed by investigator using RANO-BM Time: 36 monthsDescription: DCR for Intracranial lesions assessed by investigator using RANO-BM
Measure: DCR for Intracranial lesions assessed by investigator using RANO-BM Time: 36 monthsDescription: DoR for Intracranial lesions assessed by investigator using RANO-BM
Measure: DoR for Intracranial lesions assessed by investigator using RANO-BM Time: 36 monthsDescription: Overall Survival
Measure: Overall Survival Time: 36 monthsDescription: The 30-items questionnaire measures cancer patients' functioning and symptoms. The scale range of EORTC QLQ-C30 is 30-126. Lower values represent a better outcome.
Measure: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Time: 36 monthsDescription: The 20-items questionnaire was used among brain cancer patients. The scale range of EORTC BN20 is 20-80. Lower values represent a better outcome.
Measure: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20). Time: 36 monthsDescription: Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)
Measure: Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE) Time: 36 monthsDescription: Neurological function improvement rate assessed by RANO-BM criteria
Measure: Neurological function improvement rate assessed by RANO-BM criteria Time: 36 monthsDescription: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measure: Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0 Time: 36 monthsDescription: Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0
Measure: Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0 Time: 36 monthsDescription: Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0
Measure: Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0 Time: 36 monthsDescription: Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0
Measure: Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0 Time: 36 monthsDescription: Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0
Measure: Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0 Time: 36 monthsDescription: Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.
Measure: Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period. Time: 36 monthsDescription: Systolic and Diastolic Blood Pressure assessed during the study period.
Measure: Systolic and Diastolic Blood Pressure assessed during the study period. Time: 36 monthsDescription: Pulse rate to assessed during the study period.
Measure: Pulse rate assessed during the study period. Time: 36 monthsDescription: Body temperature assessed during the study period.
Measure: Body temperature assessed during the study period. Time: 36 monthsDescription: Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1.
Measure: PFS assess by BICR Time: 36 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1.. Inclusion Criteria: 1. Properly completed patient informed consent 2. Male or female aged at least 18 years 3. Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR mutations including L858R and/or Exon19Del. --- L858R ---
Inclusion Criteria: 1. Properly completed patient informed consent 2. Male or female aged at least 18 years 3. Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR mutations including L858R and/or Exon19Del. --- L858R ---
Eligible patients with documented EGFR mutation+ (L858R and/or Exon 19Del) TKI-naïve advanced NSCLC and documented intracranial disease will be enrolled. --- L858R ---