A global study to assess the effects of osimertinib following chemoradiation in patients with Stage III unresectable non-small cell lung cancer (LAURA) - LAURA

Study identifier:D5160C00048

ClinicalTrials.gov identifier:NCT03521154

EudraCT identifier:2018-001061-16

CTIS identifier:2022-500860-36-00

Recruitment Complete

Official Title

A Phase III, randomized, double-blind, placebo-controlled, multicenter, international study of osimertinib as maintenance therapy in patients with locally advanced, unresectable EGFR mutation-positive Non-Small Cell Lung Cancer (Stage III) whose disease has not progressed following definitive platinum-based chemoradiation therapy (LAURA).

Medical condition

Non Small Cell Lung Cancer (Stage III)

Phase

Phase 3

Healthy volunteers

Study drug

Osimertinib 80mg/40mg, Placebo Osimertinib 80mg/40mg

Sex

All

Actual Enrollment

216

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 19 Jul 2018

Primary Completion Date: 05 Jan 2024

Estimated Study Completion Date: 29 Jun 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jun 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Male or female aged at least 18 years.
2. Patients with histologically documented NSCLC of predominantly non-squamous Pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
3. The tumor harbours one of the two common EGFR mutations known to
be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone
or in combination with other EGFR mutations, assessed by cobas® EGFR
Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA
certified (USA sites) or an accredited local laboratory (sites outside of
the USA) or by central testing (cobas® v2 only).
4. Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy).
5. Chemoradiation must be completed ≤6 weeks prior to randomization.
6. Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy.
7. World Health Organization (WHO) performance status of 0 or 1.
8. Life expectancy >12 weeks at Day 1.
9. Female patients who are not abstinent (in line with the preferred and usual lifestyle choice) must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-childbearing potential.

Exclusion Criteria

1. Mixed small cell and non-small cell lung cancer histology
2. History of interstitial lung disease (ILD) prior to chemoradiation
3. Symptomatic pneumonitis following chemoradiation
4. Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > Grade 2 from the prior chemoradiation therapy
5. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
- Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long 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
6. Inadequate bone marrow reserve or organ function
7. History of other malignancies, except: adequately treated non-melanoma skin cancer or lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
8. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
9. 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
10. Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease).
11. Prior treatment with EGFR-TKI therapy
12. Major surgery as defined by the investigator within 4 weeks of the first dose of study drug.
13. Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug).
14. Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies

Location

Research Site

Atlanta, GA, United States, 30322

Location

Research Site

Mueang, Thailand, 50200

Location

Research Site

ANKARA, Turkey

Location

Research Site

Istanbul, Turkey, 34030

Location

Research Site

Ankara, Turkey, 06280

Location

Research Site

Izmir, Turkey, 35620

Location

Research Site

Istanbul, Turkey, 34854

Location

Research Site

Ankara, Turkey, 6200

Arms	Assigned Interventions
Experimental: Osimertinib Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.	Drug: Osimertinib 80mg/40mg The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Placebo Comparator: Placebo Osimertinib Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule	Drug: Placebo Osimertinib 80mg/40mg The initial dose of Placebo Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients assigned to osimertinib may continue to receive osimertinib if, in the opinion of their treating physician, they are continuing to derive clinical benefit. Patients receiving placebo may receive open-label osimertinib, in accordance with local clinical practice and the judgement of their treating physician. For all patients, post-progression treatment with AZ-supply osimertinib may continue as long as the treating physician considers the patient to be deriving clinical benefit

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Patients assigned to osimertinib may continue to receive osimertinib if, in the opinion of their treating physician, they are continuing to derive clinical benefit. Patients receiving placebo may receive open-label osimertinib, in accordance with local clinical practice and the judgement of their treating physician. For all patients, post-progression treatment with AZ-supply osimertinib may continue as long as the treating physician considers the patient to be deriving clinical benefit

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Participant Flow: Overall Study

	Osimertinib	Placebo
STARTED	143	73
COMPLETED	32	21
NOT COMPLETED	111	52
Ongoing study at data cut-off	111	52

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Baseline Measures

	Osimertinib	Placebo	Total
Number of Participants [units: Participants]	143	73	216
Age Continuous [units: Years] Median ( Full Range )	62 (36 to 84)	64 (37 to 83)	62.5 (36 to 84)
Sex: Female, Male [units: participants]
Female	90	42	132
Male	53	31	84
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	11	2	13
Not Hispanic or Latino	132	71	203
Unknown or Not Reported	0	0	0
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	2	1	3
Asian	116	62	178
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	20	10	30
More than one race	0	0	0
Unknown or Not Reported	5	0	5

Outcome Measures

1. Primary Outcome Measure: Progression-free survival (PFS) by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Primary
Measure Name	Progression-free survival (PFS) by blinded independent central review (BICR)
Measure Description	Time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Progression-free survival (PFS) by blinded independent central review (BICR) [units: Months] Median (95% Confidence Interval)	39.13 (31.51 to NA) ^[1]	5.55 (3.71 to 7.43)

Statistical Analysis 1 for Progression-free survival (PFS) by blinded independent central review (BICR)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.16
95% Confidence Interval	( 0.10 to 0.24 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

2. Secondary Outcome Measure: Number of participants with progression-free survival (PFS) events in patients with EGFR Ex19del or L858R mutation [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Number of participants with progression-free survival (PFS) events in patients with EGFR Ex19del or L858R mutation
Measure Description	Number of PFS events (PFS is time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1)
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Number of participants with progression-free survival (PFS) events in patients with EGFR Ex19del or L858R mutation [units: Participants]
Ex19Del positive	26	39
L858R positive	31	24
Missing	0	0

Statistical Analysis 1 for Number of participants with progression-free survival (PFS) events in patients with EGFR Ex19del or L858R mutation

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazard model]
Hazard Ratio (HR)^[5]	0.17
95% Confidence Interval	( 0.10 to 0.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	PFS in Ex19Del positive patients
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

Statistical Analysis 2 for Number of participants with progression-free survival (PFS) events in patients with EGFR Ex19del or L858R mutation

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazard model]
Hazard Ratio (HR)^[5]	0.32
95% Confidence Interval	( 0.19 to 0.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	PFS in L858R positive patients
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

3. Secondary Outcome Measure: Number of participants with progression-free survival (PFS) events in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Number of participants with progression-free survival (PFS) events in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA
Measure Description	Number of PFS events (PFS is time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review (BICR) assessment according to RECIST v1.1)
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Number of participants with progression-free survival (PFS) events in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA [units: Participants]
EGFR mutation-positive	4	4
EGFR mutation-negative	42	51
EGFR mutation-unknown	11	8

Statistical Analysis 1 for Number of participants with progression-free survival (PFS) events in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazard model]
Hazard Ratio (HR)^[5]	0.22
95% Confidence Interval	( 0.15 to 0.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Negative at screening
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

4. Secondary Outcome Measure: Central nervous system (CNS) progression-free survival (PFS) by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Central nervous system (CNS) progression-free survival (PFS) by blinded independent central review (BICR)
Measure Description	Time from randomisation until the date of CNS disease progression or death (by any cause in the absence of CNS progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on CNS BICR assessment according to RECIST v1.1
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Central nervous system (CNS) progression-free survival (PFS) by blinded independent central review (BICR) [units: Months] Median (95% Confidence Interval)	NA (NA to NA) ^[1]	14.88 (7.36 to NA) ^[1]

Statistical Analysis 1 for Central nervous system (CNS) progression-free survival (PFS) by blinded independent central review (BICR)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.17
95% Confidence Interval	( 0.09 to 0.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

5. Secondary Outcome Measure: Overall survival (count) [ Time Frame: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Overall survival (count)
Measure Description	Number of patients with Overall Survival (OS), the time from the date of randomisation until date of death by any cause
Time Frame	Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Overall survival (count) [units: Participants]
Died	28	15
Censored (includes participants still in survival follow up and terminated prior to death)	115	58

No statistical analysis provided for Overall survival (count)

6. Secondary Outcome Measure: Overall survival (duration) [ Time Frame: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Overall survival (duration)
Measure Description	Time from the date of randomisation until death by any cause
Time Frame	Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Overall survival (duration) [units: Months] Median (95% Confidence Interval)	53.95 (46.49 to NA) ^[1]	NA (42.05 to NA) ^[1]

Statistical Analysis 1 for Overall survival (duration)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.530
Hazard Ratio (HR)^[5]	0.81
95% Confidence Interval	( 0.42 to 1.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

7. Secondary Outcome Measure: Objective response rate by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Objective response rate by blinded independent central review (BICR)
Measure Description	Percentage of evaluable patients with at least one BICR assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target lesions (TL) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm. PR defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline sum of diameters). Responses include both confirmed and unconfirmed BICR responses
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Objective response rate by blinded independent central review (BICR) [units: % of participants] Number (95% Confidence Interval)	57.3 (48.8 to 65.6)	32.9 (22.3 to 44.9)

Statistical Analysis 1 for Objective response rate by blinded independent central review (BICR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	2.77
95% Confidence Interval	( 1.54 to 5.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio > 1 favours osimertinib

8. Secondary Outcome Measure: Duration of response, unconfirmed by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Duration of response, unconfirmed by blinded independent central review (BICR)
Measure Description	Date of PFS event - date of first unconfirmed response + 1 day (and expressed in months) for unconfirmed responses only
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	82	24
Duration of response, unconfirmed by blinded independent central review (BICR) [units: Months] Median (Inter-Quartile Range)	36.9 (17.9 to NA) ^[1]	6.5 (3.2 to 9.0)

No statistical analysis provided for Duration of response, unconfirmed by blinded independent central review (BICR)

9. Secondary Outcome Measure: Disease control rate by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Disease control rate by blinded independent central review (BICR)
Measure Description	Percentage of patients who have a best overall response of complete response (CR), partial response (PR) or stable disease (SD) as assessed by BICR
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Disease control rate by blinded independent central review (BICR) [units: % of participants] Number (95% Confidence Interval)	88.8 (82.5 to 93.5)	79.5 (68.4 to 88.0)

Statistical Analysis 1 for Disease control rate by blinded independent central review (BICR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.069
Odds Ratio (OR)^[5]	2.06
95% Confidence Interval	( 0.94 to 4.47 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio > 1 favours osimertinib.

10. Secondary Outcome Measure: Tumour shrinkage by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Tumour shrinkage by blinded independent central review (BICR)
Measure Description	Depth of response (or tumour shrinkage or change in tumour size) was assessed using BICR responses in target lesions. The best change in tumour size is the largest decrease from baseline or the smallest increase from baseline in the absence of a reduction
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	133	70
Tumour shrinkage by blinded independent central review (BICR) [units: % change from baseline] Median (Full Range)	-43.3 (-100 to 144)	-21.9 (-100 to 23)

No statistical analysis provided for Tumour shrinkage by blinded independent central review (BICR)

11. Secondary Outcome Measure: Proportion with tumour shrinkage by blinded independent central review (BICR) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Proportion with tumour shrinkage by blinded independent central review (BICR)
Measure Description	Proportion with depth of response (or tumour shrinkage or change in tumour size)
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Proportion with tumour shrinkage by blinded independent central review (BICR) [units: Proportion of participants]
Proportion with reduction	0.92	0.83
Proportion with reduction > 30%	0.65	0.40
Proportion with reduction > 50%	0.43	0.11
Proportion with reduction > 75%	0.18	0.09

No statistical analysis provided for Proportion with tumour shrinkage by blinded independent central review (BICR)

12. Secondary Outcome Measure: Time to death or distant metastases by blinded independent central review (BICR) [ Time Frame: Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Time to death or distant metastases by blinded independent central review (BICR)
Measure Description	Time from the date of randomisation until the first date of distant metastases or date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is detected on a scan that is anywhere other than lung or regional lymph node according to RECIST v1.1 or proven by biopsy
Time Frame	Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Time to death or distant metastases by blinded independent central review (BICR) [units: Months] Median (95% Confidence Interval)	NA (39.29 to NA) ^[1]	13.04 (9.03 to NA) ^[1]

Statistical Analysis 1 for Time to death or distant metastases by blinded independent central review (BICR)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.21
95% Confidence Interval	( 0.11 to 0.38 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

13. Secondary Outcome Measure: Time to study treatment discontinuation [ Time Frame: Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Time to study treatment discontinuation
Measure Description	Time from randomisation to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death (i.e. date of study treatment discontinuation/death or censoring – date of randomisation + 1 day, expressed in months)
Time Frame	Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Time to study treatment discontinuation [units: Months] Median (95% Confidence Interval)	40.28 (32.72 to NA) ^[1]	8.31 (6.14 to 11.10)

Statistical Analysis 1 for Time to study treatment discontinuation

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.21
95% Confidence Interval	( 0.14 to 0.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

14. Secondary Outcome Measure: Time to First Subsequent Treatment [ Time Frame: Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Time to First Subsequent Treatment
Measure Description	Time from the date of randomisation to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death
Time Frame	Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Time to First Subsequent Treatment [units: Months] Median (95% Confidence Interval)	43.83 (38.87 to NA) ^[1]	9.46 (6.60 to 11.53)

Statistical Analysis 1 for Time to First Subsequent Treatment

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.13
95% Confidence Interval	( 0.08 to 0.21 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

15. Secondary Outcome Measure: Time to second subsequent treatment [ Time Frame: Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Time to second subsequent treatment
Measure Description	Time from the date of randomisation to the earlier of the second subsequent anti-cancer therapy start date following study drug discontinuation or death
Time Frame	Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Time to second subsequent treatment [units: Months] Median (95% Confidence Interval)	NA (44.42 to NA) ^[1]	47.38 (34.14 to NA) ^[1]

Statistical Analysis 1 for Time to second subsequent treatment

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.022
Hazard Ratio (HR)^[5]	0.51
95% Confidence Interval	( 0.28 to 0.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

16. Secondary Outcome Measure: Second progression-free survival (PFS2) [ Time Frame: Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months ]

Measure Type	Secondary
Measure Name	Second progression-free survival (PFS2)
Measure Description	Time from randomisation to the earliest progression event following first objective disease progression, subsequent to the first subsequent therapy, or death.
Time Frame	Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Measured Values

	Osimertinib	Placebo
Number of Participants Analyzed [units:participants]	143	73
Second progression-free survival (PFS2) [units: Months] Median (95% Confidence Interval)	48.20 (44.42 to NA) ^[1]	47.38 (28.22 to NA) ^[1]

Statistical Analysis 1 for Second progression-free survival (PFS2)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.088
Hazard Ratio (HR)^[5]	0.62
95% Confidence Interval	( 0.35 to 1.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours osimertinib

Serious Adverse Events

Time Frame	From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug.
Additional Description	The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Serious Adverse Events

Osimertinib

Placebo

Total, serious adverse events

# participants affected / at risk

55/143 (38.46%)

11/73 (15.07%)

Gastrointestinal disorders

Large intestine polyp¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Gastrointestinal disorders

Oesophageal stenosis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Hepatobiliary disorders

Hepatic failure¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Bacterial pyelonephritis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Biliary tract infection¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Chronic hepatitis b¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Dengue fever¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

2/143 (1.40%)

0/73 (0.00%)

# events

Infections and infestations

Pneumocystis jirovecii pneumonia¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

7/143 (4.90%)

3/73 (4.11%)

# events

Infections and infestations

Pneumonia aspiration¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Infections and infestations

Pneumonia viral¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Injury, poisoning and procedural complications

Meniscus injury¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹,^†

# participants affected / at risk

15/143 (10.49%)

2/73 (2.74%)

# events

Injury, poisoning and procedural complications

Road traffic accident¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Injury, poisoning and procedural complications

Upper limb fracture¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign ovarian tumour¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bowen's disease¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Cardiac disorders

Aortic valve disease¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small intestine carcinoma¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Renal and urinary disorders

Prerenal failure¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Renal and urinary disorders

Ureterolithiasis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Reproductive system and breast disorders

Uterine prolapse¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/143 (0.70%)

1/73 (1.37%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

2/143 (1.40%)

0/73 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax spontaneous¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

1/143 (0.70%)

1/73 (1.37%)

# events

Cardiac disorders

Myocardial ischaemia¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Vascular disorders

Aortic aneurysm rupture¹,^†

# participants affected / at risk

0/143 (0.00%)

1/73 (1.37%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

Vascular disorders

Venous thrombosis limb¹,^†

# participants affected / at risk

1/143 (0.70%)

0/73 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1

Other Adverse Events

Time Frame	From the time of signature of informed consent throughout the treatment period (maximum actual duration of 62.4 and 56.2 months for Osimertinib and Placebo respectively) up to and including 28 day follow up following last dose of study drug.
Additional Description	The initial dose of osimertinib/placebo 80 mg QD could be reduced to 40 mg QD to allow for management of study treatment-related toxicities. Once the dose of osimertinib/placebo was reduced to 40 mg QD, the patient was to remain on the reduced dose until termination from study treatment

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Osimertinib	80mg once daily tablet
Placebo	Matching Placebo

Other Adverse Events

Osimertinib

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

129/143 (90.21%)

54/73 (73.97%)

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

17/143 (11.89%)

2/73 (2.74%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

13/143 (9.09%)

3/73 (4.11%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

28/143 (19.58%)

6/73 (8.22%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

13/143 (9.09%)

2/73 (2.74%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

8/143 (5.59%)

0/73 (0.00%)

# events

Infections and infestations

Paronychia¹,^†

# participants affected / at risk

24/143 (16.78%)

1/73 (1.37%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

10/143 (6.99%)

3/73 (4.11%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

10/143 (6.99%)

1/73 (1.37%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

11/143 (7.69%)

2/73 (2.74%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹,^†

# participants affected / at risk

55/143 (38.46%)

26/73 (35.62%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

10/143 (6.99%)

2/73 (2.74%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

8/143 (5.59%)

1/73 (1.37%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

8/143 (5.59%)

0/73 (0.00%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

17/143 (11.89%)

2/73 (2.74%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

21/143 (14.69%)

4/73 (5.48%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

10/143 (6.99%)

6/73 (8.22%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

5/143 (3.50%)

9/73 (12.33%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

5/143 (3.50%)

6/73 (8.22%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/143 (1.40%)

4/73 (5.48%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

23/143 (16.08%)

7/73 (9.59%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

8/143 (5.59%)

5/73 (6.85%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

7/143 (4.90%)

4/73 (5.48%)

# events

Skin and subcutaneous tissue disorders

Dermatitis acneiform¹,^†

# participants affected / at risk

9/143 (6.29%)

2/73 (2.74%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

18/143 (12.59%)

4/73 (5.48%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

18/143 (12.59%)

5/73 (6.85%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

34/143 (23.78%)

10/73 (13.70%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

8/143 (5.59%)

1/73 (1.37%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

51/143 (35.66%)

10/73 (13.70%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data

As per CSP Section 7.2, patient monitoring during treatment with open-label osimertinib is monitored by the investigator per local clinical guidance. Serious AEs and AESIs are reported in the eCRF but were not analyzed/tabulated at the time of primary analysis. Safety assessments are to be performed as per local clinical practice and not collected as part of study data capture in line with the protocol.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

D5160C00048_CSP_redacted
Download
D5160C00048_SAP_redacted
Download
D5160C00048_CSR synopsis_redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Suresh S Ramalingam

Emory University School of Medicine, Atlanta, U.S.

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D5160C00048_CSP_redacted

D5160C00048_SAP_redacted

D5160C00048_CSR synopsis_redacted

Trial Results Summaries