Register a trial

The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.


With activity expected to increase on the ANZCTR again, there may be extended wait times while we process pending studies, with priority being given to those trials submitted in February. Thank you for your patience.


Reset your password and enable multi-factor authentication (MFA)


For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.


  1. Go to the Login page, click ‘reset password’ and follow the instructions.
  2. Check your email for the link to set a new password.
  3. Create a new password that meets requirements.
  4. Return to the Login page and enter your new password. A verification code will be sent to your email.
  5. Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04035486




Registration number
NCT04035486
Ethics application status
Date submitted
27/06/2019
Date registered
29/07/2019

Titles & IDs
Public title
A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)
Scientific title
A Phase III, Open-label, Randomized Study of Osimertinib With or Without Platinum Plus Pemetrexed Chemo, as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA2).
Secondary ID [1] 0 0
2019-000650-61
Secondary ID [2] 0 0
D5169C00001
Universal Trial Number (UTN)
Trial acronym
FLAURA2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Osimertinib
Treatment: Drugs - Pemetrexed/Carboplatin
Treatment: Drugs - Pemetrexed/Cisplatin

Active comparator: Osimertinib 80mg QD - Osimertinib (AZD9291) 80mg QD.

All patients randomized into this will only receive Osimertinib 80mg.

Dose may be reduced to allow for the management of IP related toxicity.

Experimental: Osimertinib 80 mg QD and platinum-based chemotherapy - Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Dose may be reduced to allow for the management of IP related toxicity.


Treatment: Drugs: Osimertinib
Drug: Osimertinib (Oral)

Other Names:

AZD9291

Treatment: Drugs: Pemetrexed/Carboplatin
Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Treatment: Drugs: Pemetrexed/Cisplatin
Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events Graded by Common Terminology Criteria for Adverse Event v5 (Safety Run-In Treatment Arms Only)
Assessment method [1] 0 0
Adverse events were summarized by maximum reported Common Terminology Criteria for Adverse Event (CTCAE) grade, version 5.0. Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 (Severe or medically significant but not immediately life-threatening): hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 (Life-threatening consequences): urgent intervention indicated. Grade 5: Death related to AE. Includes adverse events with onset date on or after the date of first dose and up to and including 28 days following discontinuation of treatment but prior to the start of a new anti-cancer therapy.
Timepoint [1] 0 0
From first dose date to 28 days following last dose, up to 45 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) (Randomized Component)
Assessment method [2] 0 0
Progression-free survival (PFS) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. The primary efficacy analysis of the investigator-assessed progression-free survival will be performed when approximately 278 PFS events and at least 16 months of follow-up after Last subject in, has occurred in the 556 randomized patients.
Timepoint [2] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.3 months)
Primary outcome [3] 0 0
Sensitivity Analysis for Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment (Randomized Component)
Assessment method [3] 0 0
Sensitivity analysis for progression-free survival (PFS) by blinded independent central review (BICR) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. The primary efficacy analysis of the investigator-assessed progression-free survival will be performed when approximately 278 PFS events and at least 16 months of follow-up after Last subject in, has occurred in the 556 randomized patients.
Timepoint [3] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.2 months).
Secondary outcome [1] 0 0
Overall Survival (OS) (Safety Run-In Treatment Arms Only)
Assessment method [1] 0 0
Overall survival is defined as the time from the date of first dose until death due to any causes. Subjects not known to have died at the time of analysis are censored at the last recorded date on which the subject was known to be alive. Median overall survival calculated using the Kaplan-Meier method. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.
Timepoint [1] 0 0
Up to 45 months (maximum follow up 44.6 months)
Secondary outcome [2] 0 0
Duration of Response (DoR) (Safety Run-In Treatment Arms Only)
Assessment method [2] 0 0
Duration of response (DoR) is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression (i.e. date of progression free survival event or censoring - date of first response + 1). The end of response should coincide with the date of progression or death from any cause used for the progression free survival endpoint. The time of the initial response is defined as the latest of the dates contributing towards the first visit that was Complete response or Partial response that was subsequently confirmed. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.
Timepoint [2] 0 0
Up to 45 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) (Safety Run-In Treatment Arms Only)
Assessment method [3] 0 0
Confirmed objective response rate (per RECIST 1.1 using Investigator assessments) is defined as the number (%) of subjects with at least 1 visit response of Completed Response (CR) or Partial Response (PR), where each CR or PR must be subsequently confirmed at least 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and CR/PR confirmation visit. Confidence Interval is calculated using the exact Clopper-Pearson method. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.
Timepoint [3] 0 0
Up to 45 months
Secondary outcome [4] 0 0
Depth of Response (Percent Change From Baseline in Tumor Diameter) (Safety Run-In Treatment Arms Only)
Assessment method [4] 0 0
Depth of Response (percent change from Baseline in tumor diameter) is defined as the relative percent change in the sum of the longest diameters of RECIST 1.1 target lesions (TL) at the nadir in the absence of new lesions or progression of non-target lesions (NTL) compared to baseline. The best percentage change in TL size is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. Tumor assessments of the chest and abdomen (including the entire liver and both adrenal glands) were performed using RECIST 1.1 by the investigator on images from CT (preferred) or MRI with IV contrast. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.
Timepoint [4] 0 0
Up to 45 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR) by Investigator (Safety Run-In Treatment Arms Only)
Assessment method [5] 0 0
Disease control rate is defined as the percentage of subjects who have a best overall response of Complete response (CR) or Partial response (PR) or Stable disease (SD) by RECIST 1.1 as assessed by the Investigator. For participants with a best overall response of SD, a RECIST assessment of SD must have been observed at least 6 weeks minus 1 week (at least 35 study days) following the first dose. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.
Timepoint [5] 0 0
Up to 45 months
Secondary outcome [6] 0 0
Overall Survival (OS) (Randomized Component)
Assessment method [6] 0 0
Overall survival is defined as the time from the date of randomization until death due to any cause. Subjects not known to have died at the time of analysis are censored at the last recorded date on which the subject was known to be alive. Median overall Survival calculated using the Kaplan-Meier method.
Timepoint [6] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)
Secondary outcome [7] 0 0
Landmark Overall Survival (LOS) at 1, 2, and 3 Years (Randomized Component)
Assessment method [7] 0 0
Landmark Overall Survival at 1, 2, and 3 years looks at the percent of patients alive at 1, 2 and 3 year time points. Overall survival at 36 months not included to data cut off prior to 36-month timepoint. Overall survival percentage calculated using the Kaplan-Meier method.
Timepoint [7] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)
Secondary outcome [8] 0 0
Objective Response Rate (ORR) (Randomized Component)
Assessment method [8] 0 0
Objective Response Rate (ORR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments) is defined as the number (%) of patients with at least 1 visit response of Complete Response or Partial Response. Data obtained up until progression, or the last evaluable assessment in the absence of progression, was included in the assessment of Objective Response Rate. The investigator-assessed ORR was summarized with a logistic regression stratified by race (Chinese/Asian vs. Non-Chinese/Asian vs. Non-Asian), WHO performance status (0 vs. 1), and method used for tissue testing (central vs. local).
Timepoint [8] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [9] 0 0
Duration of Response (DoR) (Randomized Component)
Assessment method [9] 0 0
The duration of response is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the progression-free survival endpoint. The time of the initial response is defined as the latest of the dates contributing towards the first response of Partial response or Complete response. Median values of the duration of response, along with two-sided 95% CI in each treatment group were computed using the Kaplan-Meier method.
Timepoint [9] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [10] 0 0
Depth of Response (Percent Change From Baseline in Tumor Diameter) (Randomized Component)
Assessment method [10] 0 0
Depth of Response (percent change from Baseline in tumor diameter) is defined as the relative percent change in the sum of the longest diameters of RECIST 1.1 target lesions (TL) at the nadir in the absence of new lesions or progression of non-target lesions (NTL) compared to baseline. The best percentage change in TL size is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. Tumor assessments of the chest and abdomen (including the entire liver and both adrenal glands) were performed using RECIST 1.1 by the investigator on images from CT (preferred) or MRI with IV contrast.
Timepoint [10] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [11] 0 0
Disease Control Rate (DCR) by Investigator (Randomized Component)
Assessment method [11] 0 0
Disease control rate (DCR) is defined as the percentage of subjects who have a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the Investigator. For participants with a best overall response of SD, a RECIST assessment of SD must have been observed at least 6 weeks minus 1 week (at least 35 study days) following the randomization. The adjusted disease control rate was calculated using a logistic regression stratified by race (Chinese/Asian vs. Non-Chinese/Asian vs. Non-Asian), WHO performance status (0 vs. 1), and method used for tissue testing (central vs. local).
Timepoint [11] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [12] 0 0
Progression Free Survival 2 (PFS2) (Randomized Component)
Assessment method [12] 0 0
Progression Free Survival 2 is defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary Progression Free Survival (PFS), or death in absence of a first or second progression. The second progression event must have occurred after subsequent treatment administered after the initial progression free survival event. Any participant that was lost to follow-up, withdrew consent or discontinued for other reasons at the time of the analysis were censored at the last evaluable progression assessment. Median second progression free survival (months) calculated using the Kaplan-Meier method.
Timepoint [12] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [13] 0 0
Time to First Subsequent Therapy (TFST) or Death (Randomized Component)
Assessment method [13] 0 0
Time to first subsequent therapy (TFST) or death is defined as the time from the date of randomization to the earlier of the date of anti- cancer therapy start date following IP discontinuation or death. Any patient not known to have had a subsequent therapy or not known to have died at the time of the analysis were censored at the last known time to have not received subsequent therapy; i.e., the last follow-up visit where this was confirmed. Median time to first subsequent therapy or death calculated using the Kaplan-Meier method.
Timepoint [13] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [14] 0 0
Time to Second Subsequent Therapy (TSST) or Death (Randomized Component)
Assessment method [14] 0 0
Time to second subsequent therapy (TSST) or death is defined as the time from the date of randomization to the earlier of the date of second subsequent anti-cancer therapy start date following IP discontinuation or death. Any patient not known to have died at the time of the analysis and not known to have had a second subsequent therapy will be censored at the last known time to have not received second subsequent therapy, i.e., the last follow-up visit where this was confirmed. If a patient terminated the study for reason other than death before second subsequent therapy, these patients will be censored at the earliest of their last known to be alive and termination dates. Median time to second subsequent therapy or death calculated using the Kaplan-Meier method.
Timepoint [14] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [15] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) (Randomized Component)
Assessment method [15] 0 0
QLQ-C30 has 30 questions and scores range from 0-100 after a linear transformation. Questions are combined to produce symptom scales, individual symptom items, functional scales, and global health status (GHS)/quality of life (QoL). Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status. The score values calculated by averaging across patients overall mean across all visits. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (random effect), treatment, visit (fixed effect \& repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction.
Timepoint [15] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [16] 0 0
Median Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) (Randomized Component)
Assessment method [16] 0 0
The EORTC QLQ-C30 consists of 30 questions that are combined to produce 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), 5 functional scales (physical, role, cognitive, emotional, and social), and a global measure of health status/QoL. Scores range from 0-100 after a linear transformation. Time to deterioration (TTD) is defined as the time from randomization until the date of the first clinically meaningful worsening (a change in the score from baseline of =10) that is confirmed at a subsequent assessment or death in the absence of a clinically meaningful symptom, function, or global health status/QoL worsening, regardless of whether the patient withdraws from study treatment or receives another anticancer therapy prior to symptom, function or GHS/QoL deterioration. The median TTD was calculated using the Kaplan-Meier method.
Timepoint [16] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [17] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Items (EORTC QLQ-LC13) (Randomized Component)
Assessment method [17] 0 0
EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. While the QLQ-LC13 includes more scales, only the Coughing, Pain in chest, and Dyspnea subscale scores were analyzed for this endpoint. Negative change from baseline scores indicates less symptom severity, and thus improvement on health status. The score values calculated by averaging across patients overall mean across all visits. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (as a random effect), treatment, visit (as fixed effect and repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction.
Timepoint [17] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [18] 0 0
Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Items (EORTC QLQ-LC13) (Randomized Component)
Assessment method [18] 0 0
EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. Time to deterioration (TTD) is defined as the time from randomization until the date of the first clinically meaningful worsening (a change in the score from baseline of =10) that is confirmed at a subsequent assessment or death in the absence of a clinically meaningful symptom, function, or global health status/QoL worsening, regardless of whether the patient withdraws from study treatment or receives another anticancer therapy prior to symptom, function or GHS/QoL deterioration. The median TTD was calculated using the Kaplan-Meier method.
Timepoint [18] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [19] 0 0
Concordance of Epidermal Growth Factor Receptor (EGFR) Mutation Status Between the Local EGFR Mutation Test and the Central Cobas® EGFR Mutation Test v2 Results: Exon 19 Deletion (Randomized Component)
Assessment method [19] 0 0
Comparing the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results in participants with EXON 19 Deletion, excluding invalid results. Since this endpoint uses pre-randomization data to compare results from a central vs. local lab, randomized component treatment arms were combined for analysis.
Timepoint [19] 0 0
Screening/Baseline
Secondary outcome [20] 0 0
Concordance of Epidermal Growth Factor Receptor (EGFR) Mutation Status Between the Local EGFR Mutation Test and the Central Cobas® EGFR Mutation Test v2 Results: L858R (Randomized Component)
Assessment method [20] 0 0
Comparing the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results in participants with L858R, excluding invalid results. Since this endpoint uses pre-randomization data to compare results from a central vs. local lab, randomized component treatment arms were combined for analysis.
Timepoint [20] 0 0
Screening/Baseline
Secondary outcome [21] 0 0
Progression-free Survival (PFS) by Investigator by Plasma Epidermal Growth Factor Receptor Mutation Status: Exon 19 Deletion - Participants With an Event (Randomized Component)
Assessment method [21] 0 0
PFS is defined as the time from randomization until an event. An event is defined as the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the subject withdraws from study treatment or receives another anti-cancer therapy prior to progression. Subgroup analysis was performed using a Cox proportional hazards model including treatment, subgroup and a treatment-by subgroup interaction term.
Timepoint [21] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [22] 0 0
Progression-free Survival (PFS) by Investigator by Plasma Epidermal Growth Factor Receptor Mutation Status: L858R - Participants With an Event (Randomized Component)
Assessment method [22] 0 0
PFS is defined as the time from randomization until an event. An event is defined as the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the subject withdraws from study treatment or receives another anti-cancer therapy prior to progression. Subgroup analysis was performed using a Cox proportional hazards model including treatment, subgroup and a treatment-by subgroup interaction term.
Timepoint [22] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [23] 0 0
Plasma Concentration of Osimertinib When Given With or Without Chemotherapy (Randomized Component)
Assessment method [23] 0 0
An analysis will be performed to assess whether the plasma concentration of osimertinib is affected when given with or without chemotherapy. Samples were collected pre-dose and 1-hour post-dose on day 22 and day 106; on day 43 samples were collected pre-dose and 1-, 2-, 4-, and 6-hours post-dose.
Timepoint [23] 0 0
Pre-dose and 1-hour post-dose on Day 22; pre-dose, 1-, 2-, 4-, and 6-hours post-dose on Day 43; pre-dose and 1-hour post-dose on Day 106.
Secondary outcome [24] 0 0
Plasma Concentration of Metabolite AZ5104 When Osimertinib is Given With or Without Chemotherapy (Randomized Component)
Assessment method [24] 0 0
An analysis will be performed to assess whether the plasma concentration of metabolite AZ5104 is affected when given with or without chemotherapy. Samples were collected pre-dose and 1-hour post-dose on day 22 and day 106; on day 43 samples were collected pre-dose and 1-, 2-, 4-, and 6-hours post-dose.
Timepoint [24] 0 0
Pre-dose and 1-hour post-dose on Day 22; pre-dose, 1-, 2-, 4-, and 6-hours post-dose on Day 43; pre-dose and 1-hour post-dose on Day 106.
Secondary outcome [25] 0 0
Mean Cmin,ss and Mean Cmax,ss of Osimertinib (Randomized Component)
Assessment method [25] 0 0
Cmin,ss is the minimum plasma concentration of Osimertinib at steady state. Cmax,ss is the maximum plasma concentration of Osimertinib at steady state.
Timepoint [25] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [26] 0 0
Mean Cmin,ss and Mean Cmax,ss of AZ5104 (Randomized Component)
Assessment method [26] 0 0
Cmin,ss is the minimum plasma concentration of AZ5104 at steady state. Cmax,ss is the maximum plasma concentration of AZ5104 at steady state.
Timepoint [26] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [27] 0 0
Mean AUCss of Osimertinib (Randomized Component)
Assessment method [27] 0 0
AUCss is the area under the plasma concentration-time curve over a doing interval at a stead state.
Timepoint [27] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [28] 0 0
Mean AUCss of AZ5104 (Randomized Component)
Assessment method [28] 0 0
AUCss is the area under the plasma concentration-time curve over a doing interval at a stead state.
Timepoint [28] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [29] 0 0
Mean CLss/F of Osimertinib (Randomized Component)
Assessment method [29] 0 0
CLss/F is the apparent plasma clearance at steady state.
Timepoint [29] 0 0
Up to approximately 33 months after the first patient is randomized.

Eligibility
Key inclusion criteria
1. Male or female, at least 18 years of age; patients from Japan at least 20 years of age.
2. Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC). NSCLC of mixed histology is allowed.
3. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic Non-Small Cell Lung Cancer (NSCLC) (clinical stage IVA or IVB) or recurrent Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M.
5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
6. WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
7. Life expectancy >12 weeks at Day 1.
8. Willing to use contraception as appropriate during the study and for a period of time after discontinuing study treatment.
Minimum age
18 Years
Maximum age
110 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Spinal cord compression; and unstable brain metastases, with stable brain metastases who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids can be enrolled. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated
2. Past medical history of Interstitial Lung Disease (ILD), drug-induced Interstitial Lung Disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active Interstitial Lung Disease.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including Hep. B, Hep. C and HIV. Screening for chronic conditions is not required. Active infection will include any patients receiving treatment for infection.
4. QT prolongation or any clinically important abnormalities in rhythm.
5. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

* Absolute neutrophil count below the lower limit of normal (<LLN)
* Platelet count below the LLN
* Hemoglobin <90 g/L. The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted.
* ALT >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
* AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
* Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
* Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation or 24 hour urine collection (refer to Appendix I for appropriate calculation)
6. 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.
7. Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapies, investigational agents are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease.
8. Prior treatment with an Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).
9. Major surgery within 4 weeks of the first dose of investigational product (IP). Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery are permitted.
10. Radiotherapy treatment to more than 30% of the bone marrow or( with a wide field of radiation within 4 weeks of the first dose of investigational product (IP).
11. History of hypersensitivity to active or inactive excipients of investigational product (IP) or drugs with a similar chemical structure or class to investigational product (IP).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/06/2026
Actual
Sample size
Target
Accrual to date
Final
587
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Chermside
Recruitment hospital [3] 0 0
Research Site - Elizabeth Vale
Recruitment hospital [4] 0 0
Research Site - Heidelberg
Recruitment hospital [5] 0 0
Research Site - Kogarah
Recruitment hospital [6] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Caba
Country [15] 0 0
Argentina
State/province [15] 0 0
Ciudad de Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Argentina
State/province [17] 0 0
Santa Fe
Country [18] 0 0
Brazil
State/province [18] 0 0
Barretos
Country [19] 0 0
Brazil
State/province [19] 0 0
Florianópolis
Country [20] 0 0
Brazil
State/province [20] 0 0
Londrina
Country [21] 0 0
Brazil
State/province [21] 0 0
Porto Alegre
Country [22] 0 0
Brazil
State/province [22] 0 0
Ribeirão Preto
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Brazil
State/province [24] 0 0
São José do Rio Preto
Country [25] 0 0
Brazil
State/province [25] 0 0
São Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
Vitoria
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Chile
State/province [29] 0 0
Santiago
Country [30] 0 0
Chile
State/province [30] 0 0
Temuco
Country [31] 0 0
Chile
State/province [31] 0 0
Viña del Mar
Country [32] 0 0
China
State/province [32] 0 0
Beijing
Country [33] 0 0
China
State/province [33] 0 0
Changchun
Country [34] 0 0
China
State/province [34] 0 0
Changsha
Country [35] 0 0
China
State/province [35] 0 0
Chengdu
Country [36] 0 0
China
State/province [36] 0 0
Chongqing
Country [37] 0 0
China
State/province [37] 0 0
Guangzhou
Country [38] 0 0
China
State/province [38] 0 0
Haikou
Country [39] 0 0
China
State/province [39] 0 0
Hangzhou
Country [40] 0 0
China
State/province [40] 0 0
Harbin
Country [41] 0 0
China
State/province [41] 0 0
Hefei
Country [42] 0 0
China
State/province [42] 0 0
Jinan
Country [43] 0 0
China
State/province [43] 0 0
Nanjing
Country [44] 0 0
China
State/province [44] 0 0
Shanghai
Country [45] 0 0
China
State/province [45] 0 0
Shenyang
Country [46] 0 0
China
State/province [46] 0 0
Urumqi
Country [47] 0 0
China
State/province [47] 0 0
Wuhan
Country [48] 0 0
China
State/province [48] 0 0
Xi'an
Country [49] 0 0
China
State/province [49] 0 0
Zhengzhou
Country [50] 0 0
Czechia
State/province [50] 0 0
Olomouc
Country [51] 0 0
Czechia
State/province [51] 0 0
Ostrava - Vitkovice
Country [52] 0 0
Czechia
State/province [52] 0 0
Praha 5
Country [53] 0 0
Czechia
State/province [53] 0 0
Praha
Country [54] 0 0
France
State/province [54] 0 0
Bordeaux Cedex
Country [55] 0 0
France
State/province [55] 0 0
Lyon
Country [56] 0 0
France
State/province [56] 0 0
Montpellier
Country [57] 0 0
France
State/province [57] 0 0
Villejuif Cedex
Country [58] 0 0
India
State/province [58] 0 0
Belagavi
Country [59] 0 0
India
State/province [59] 0 0
Bengaluru
Country [60] 0 0
India
State/province [60] 0 0
Gurgaon
Country [61] 0 0
India
State/province [61] 0 0
Kolkata
Country [62] 0 0
India
State/province [62] 0 0
New Delhi
Country [63] 0 0
India
State/province [63] 0 0
Pune
Country [64] 0 0
Japan
State/province [64] 0 0
Bunkyo-ku
Country [65] 0 0
Japan
State/province [65] 0 0
Fukuoka
Country [66] 0 0
Japan
State/province [66] 0 0
Hidaka-shi
Country [67] 0 0
Japan
State/province [67] 0 0
Himeji-shi
Country [68] 0 0
Japan
State/province [68] 0 0
Iwakuni-shi
Country [69] 0 0
Japan
State/province [69] 0 0
Kanazawa
Country [70] 0 0
Japan
State/province [70] 0 0
Kashiwa
Country [71] 0 0
Japan
State/province [71] 0 0
Koto-ku
Country [72] 0 0
Japan
State/province [72] 0 0
Osaka-shi
Country [73] 0 0
Japan
State/province [73] 0 0
Sakai-shi
Country [74] 0 0
Japan
State/province [74] 0 0
Sapporo-shi
Country [75] 0 0
Japan
State/province [75] 0 0
Sendai-shi
Country [76] 0 0
Japan
State/province [76] 0 0
Sunto-gun
Country [77] 0 0
Japan
State/province [77] 0 0
Yokohama-shi
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Cheongju-si
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Goyang-si
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Seoul
Country [81] 0 0
Peru
State/province [81] 0 0
Arequipa
Country [82] 0 0
Peru
State/province [82] 0 0
Lima
Country [83] 0 0
Peru
State/province [83] 0 0
San Isidro
Country [84] 0 0
Philippines
State/province [84] 0 0
Cebu City
Country [85] 0 0
Philippines
State/province [85] 0 0
Davao City
Country [86] 0 0
Philippines
State/province [86] 0 0
Iloilo City
Country [87] 0 0
Philippines
State/province [87] 0 0
Las Pinas
Country [88] 0 0
Philippines
State/province [88] 0 0
Legazpi City
Country [89] 0 0
Philippines
State/province [89] 0 0
Quezon City
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Moscow
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Murmansk
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Saint Petersburg
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Saint-Petersburg
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Syktyvkar
Country [95] 0 0
Slovakia
State/province [95] 0 0
Bratislava
Country [96] 0 0
Slovakia
State/province [96] 0 0
Kosice
Country [97] 0 0
Slovakia
State/province [97] 0 0
Poprad
Country [98] 0 0
South Africa
State/province [98] 0 0
Johannesburg
Country [99] 0 0
South Africa
State/province [99] 0 0
Port Elizabeth
Country [100] 0 0
South Africa
State/province [100] 0 0
Rondebosch
Country [101] 0 0
Taiwan
State/province [101] 0 0
Changhua
Country [102] 0 0
Taiwan
State/province [102] 0 0
Hualien City
Country [103] 0 0
Taiwan
State/province [103] 0 0
Kaohsiung
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taichung
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taipei
Country [106] 0 0
Thailand
State/province [106] 0 0
Bangkok
Country [107] 0 0
Thailand
State/province [107] 0 0
Hat Yai
Country [108] 0 0
Thailand
State/province [108] 0 0
Khon Kaen
Country [109] 0 0
Thailand
State/province [109] 0 0
Muang
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Cambridge
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Leicester
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Liverpool
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Maidstone
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Manchester
Country [115] 0 0
Vietnam
State/province [115] 0 0
Hanoi
Country [116] 0 0
Vietnam
State/province [116] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pasi A. Jänne, MD
Address 0 0
Dana Farber Cancer Institute, 450 Brookline Avenue, LC4114, Boston, MA 02215, USA
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04035486