AZD9291 First Time In Patients Ascending Dose Study (AURA)

• ClinicalTrials.gov Identifier: NCT01802632
• Recruitment Status: Completed
• First Posted: March 1, 2013
• Results First Posted: October 6, 2016
• Last Update Posted: January 18, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Advanced Non Small Cell Lung Cancer; Advanced (Inoperable) Non Small Cell Lung Cancer
• Intervention: Drug: AZD9291
• Enrollment: 603

Participant Flow

Recruitment Details	Patients recruited to different cohorts. Dose escalation cohort of pre-treated patients in 5 dose groups. Dose expansion cohort (pre-treated) in same 5 dose groups. First line patient cohort. 80mg tablet cohort of pre-treated patients. Japan-only cohort (EGFR T790M+ by cytology). Phase II extension cohort in pre-treated EGFR T790M+ patients.
Pre-assignment Details	603 patients were enrolled and received treatment.

Arm/Group Title	AZD9291 80mg Extension	Dose Escalation	Dose Expansion	First Line	80mg Tablet	Japan Cytology
Arm/Group Description	Phase II dose extension cohort in pre-treated EGFR T790M mutation positive patients in AZD9291 80mg tablet.	Pre-treated patient cohort in doses 20, 40, 80, 160 and 240mg AZD9291 capsule.	Pre-treated EGFR T790M mutation positive (by central testing) patient cohort. Dose groups were expanded to include more patients.	Cohort of patients receiving first-line treatment for EGFRm advanced NSCLC, in 80mg and 160mg AZD9291 capsule.	US-only cohort of pre-treated EGFR patients receiving the tablet formulation of AZD9291 (80 mg).	Japan-only cohort of patients (EGFR T790M mutation status determined from cytology samples) receiving AZD9291 80 mg tablet.
Period Title: Overall Study
Started	201	31	271	60	12	28
Completed	0	0	0	0	0	0
Not Completed	201	31	271	60	12	28
Reason Not Completed
Death	28	1	38	0	2	0
Withdrawal by Subject	4	2	7	3	0	1
Objective Disease Progression	1	12	104	6	4	4
Ongoing Study at Data Cut-off	168	16	115	50	6	22
Other (not specified)	0	0	7	1	0	1

Baseline Characteristics

Arm/Group Title		AZD9291 80mg Extension	Dose Escalation	Dose Expansion	First Line	80mg Tablet	Japan Cytology	Total
Arm/Group Description		Phase II dose extension cohort in pre-treated EGFR T790M mutation positive patients in AZD9291 80mg tablet.	Pre-treated patient cohort in doses 20, 40, 80, 160 and 240mg AZD9291 capsule.	Pre-treated EGFR T790M mutation positive (by central testing) patient cohort. Dose groups were expanded to include more patients.	Cohort of patients receiving first-line treatment for EGFRm advanced NSCLC, in 80mg and 160mg AZD9291 capsule.	US-only cohort of pre-treated EGFR patients receiving the tablet formulation of AZD9291 (80 mg).	Japan-only cohort of patients (EGFR T790M mutation status determined from cytology samples) receiving AZD9291 80 mg tablet.	Total of all reporting groups
Overall Number of Baseline Participants		201	31	271	60	12	28	603
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	201 participants	31 participants	271 participants	60 participants	12 participants	28 participants	603 participants
<50 Years		30	3	42	8	3	3	89
>=50-<65 Years		86	19	142	23	6	13	289
>=65-<75 Years		64	8	59	22	3	9	165
>=75 Years		21	1	28	7	0	3	60
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	201 participants	31 participants	271 participants	60 participants	12 participants	28 participants	603 participants
	Female	133 66.2%	20 64.5%	167 61.6%	45 75.0%	8 66.7%	21 75.0%	394 65.3%
	Male	68 33.8%	11 35.5%	104 38.4%	15 25.0%	4 33.3%	7 25.0%	209 34.7%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	201 participants	31 participants	271 participants	60 participants	12 participants	28 participants	603 participants
Asian		114	21	160	43	4	28	370
Black Or African American		1	0	3	0	1	0	5
Missing		2	0	0	0	0	0	2
Not Reported		4	4	11	1	0	0	20
Other		4	1	2	1	0	0	8
White		76	5	95	14	7	0	197
American Indian or Alaska Native		0	0	0	1	0	0	1

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) for Dose Expansion Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Outcome Measure Data

Analysis Population Description

All pre-treated EGFR T790M mutation positive (by central testing) patients who received at least one dose of AZD9291.

Arm/Group Title	Dose Expansion
Arm/Group Description:	Pre-treated EGFR T790M mutation positive (by central testing) patient cohort. Dose groups were expanded to include more patients.
Overall Number of Participants Analyzed	175
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: % of participants
	61.7; (54.1 to 68.9)

2. Primary Outcome

Title	Best Objective Response (BOR) for Dose Escalation Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)

Outcome Measure Data

Analysis Population Description

All pre-treated EGFR T790M mutation positive (by central testing) patients who received at least one dose of AZD9291.

Arm/Group Title	Dose Escalation
Arm/Group Description:	Pre-treated patient cohort in doses 20, 40, 80, 160 and 240mg AZD9291 capsule.
Overall Number of Participants Analyzed	31
Measure Type: Number; Unit of Measure: % of participants
Partial Response	58.1
Stable disease	19.4
Progressive disease	16.1
Not evaluable	6.5

3. Primary Outcome

Title	Objective Response Rate (ORR) for Extension Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by independent central review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)

Outcome Measure Data

Analysis Population Description

All patients in the 80mg AZD9291 extension part of the study (second line or later, EGFR T790M mutation positive by central testing) who received at least one dose of AZD9291 and had measurable disease (by independent central review) at baseline.

Arm/Group Title	80mg AZD9291 Extension
Arm/Group Description:	Phase II dose extension cohort in pre-treated EGFR T790M mutation positive patients in AZD9291 80mg tablet.
Overall Number of Participants Analyzed	199
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: % of participants
	61.3; (54.2 to 68.1)

4. Secondary Outcome

Title	Duration of Response (DoR) for Dose Expansion Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Outcome Measure Data

Analysis Population Description

All pre-treated EGFR T790M mutation positive (by central testing) patients who received at least one dose of AZD9291.

Arm/Group Title	Dose Expansion
Arm/Group Description:	Pre-treated EGFR T790M mutation positive (by central testing) population. Dose groups were expanded to include more patients.
Overall Number of Participants Analyzed	108
Median (95% Confidence Interval); Unit of Measure: months
	11.1; (8.3 to 13.8)

5. Secondary Outcome

Title	Progression-Free Survival (PFS) for Dose Expansion Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of first dose until the date of PD (by independent central review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Outcome Measure Data

Analysis Population Description

All pre-treated EGFR T790M mutation positive (by central testing) patients who received at least one dose of AZD9291.

Arm/Group Title	Dose Expansion
Arm/Group Description:	Pre-treated EGFR T790M mutation positive (by central testing) population. Dose groups were expanded to include more patients.
Overall Number of Participants Analyzed	175
Median (95% Confidence Interval); Unit of Measure: months
	9.7; (8.3 to 12.5)

6. Secondary Outcome

Title	Best Objective Response (BOR) for 80mg AZD9291 Extension Population
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)

Outcome Measure Data

Analysis Population Description

All patients in the 80mg AZD9291 extension part of the study (second line or later, EGFR T790M mutation positive by central testing) who received at least one dose of AZD9291 and had measurable disease (by investigator assessment) at baseline.

Arm/Group Title	80mg AZD9291 Extension
Arm/Group Description:	Phase II dose extension cohort in pre-treated EGFR T790M mutation positive patients in AZD9291 80mg tablet.
Overall Number of Participants Analyzed	201
Measure Type: Number; Unit of Measure: % of participants
Complete Response	0.5
Partial response	70.1
Stable disease	22.9
Progressive disease	6.0
Not evaluable	0.5

Adverse Events

Time Frame	AEs from start of study drug until 28 days post study treatment discontinuation, up to approximately 25 months (at time of analysis).
Adverse Event Reporting Description	Different cohorts started at different times and so some cohorts have collected AE data for a shorter length of time, e.g. Extension cohort was the last cohort and follow up is approximately 12 months at time of analysis. Systematic assessment due to regular investigator assessment at study visits.
Arm/Group Title	AZD9291 80mg Extension		Dose Escalation		Dose Expansion		First Line		80mg Tablet		Japan Cytology
Arm/Group Description	Phase II dose extension cohort in pre-treated EGFR T790M mutation positive patients in AZD9291 80mg tablet.		Pre-treated patient cohort in doses 20, 40, 80, 160 and 240mg AZD9291 capsule.		Pre-treated EGFR T790M mutation positive (by central testing) patient cohort. Dose groups were expanded to include more patients.		Cohort of patients receiving first-line treatment for EGFRm advanced NSCLC, in 80mg and 160mg AZD9291 capsule.		US-only cohort of pre-treated EGFR patients receiving the tablet formulation of AZD9291 (80 mg).		Japan-only cohort of patients (EGFR T790M mutation status determined from cytology samples) receiving AZD9291 80 mg tablet.
All-Cause Mortality
	AZD9291 80mg Extension		Dose Escalation		Dose Expansion		First Line		80mg Tablet		Japan Cytology
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	AZD9291 80mg Extension		Dose Escalation		Dose Expansion		First Line		80mg Tablet		Japan Cytology
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/201 (20.40%)		9/31 (29.03%)		78/271 (28.78%)		14/60 (23.33%)		4/12 (33.33%)		4/28 (14.29%)
Blood and lymphatic system disorders
Anaemia † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Disseminated intravascular coagulation † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Thrombocytopenia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pancytopenia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cardiac disorders
Cardiac failure congestive † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cardiac failure acute † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Myocardial infarction † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pulseless electrical activity † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Stress cardiomyopathy † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Eye disorders
Corneal erosion † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Gastrointestinal disorders
Constipation † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Diarrhoea † 1	1/201 (0.50%)	1	1/31 (3.23%)	1	4/271 (1.48%)	4	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Inguinal hernia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Nausea † 1	1/201 (0.50%)	1	2/31 (6.45%)	3	3/271 (1.11%)	3	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Vomiting † 1	1/201 (0.50%)	1	1/31 (3.23%)	1	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Food poisoning † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Pancreatitis † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Abdominal pain upper † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Dysphagia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Haematemesis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Intestinal obstruction † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Oesophageal stenosis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Oesophagitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Small intestine ulcer † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
General disorders
Asthenia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Fatigue † 1	1/201 (0.50%)	1	1/31 (3.23%)	1	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Localised oedema † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Oedema peripheral † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
General physical health deterioration † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pyrexia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Hepatobiliary disorders
Hepatic function abnormal † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Jaundice † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Liver disorder † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cholangitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cholecystitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Infections and infestations
Appendicitis † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Bronchopneumonia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Influenza † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pneumonia † 1	7/201 (3.48%)	7	3/31 (9.68%)	3	8/271 (2.95%)	8	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Salmonella sepsis † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Urinary tract infection † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Urinary tract infection bacterial † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Viral infection † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Lower respiratory tract infection † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Streptococcal bacteraemia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Abscess † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Bacteraemia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Bacterial sepsis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Bronchitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cellulitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Device related infection † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Erysipelas † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Klebsiella infection † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Lung infection † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Mediastinitis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pneumonia pneumococcal † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Post procedural infection † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pyelonephritis acute † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Respiratory tract infection bacterial † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Sepsis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Septic shock † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Upper respiratory tract infection † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Urinary tract infection bacterial † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Viraemia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Injury, poisoning and procedural complications
Traumatic fracture † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Fall † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Overdose † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Spinal fracture † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Subdural haematoma † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Thoracic vertebral fracture † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Investigations
Blood bilirubin increased † 1	1/201 (0.50%)	1	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Neutrophil count decreased † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Platelet count decreased † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Alanine aminotransferase increased † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Aspartate aminotransferase increased † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/201 (0.50%)	1	2/31 (6.45%)	2	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Hyponatraemia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Dehydration † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Hypoglycaemia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Hypokalaemia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	1/28 (3.57%)	1
Costochondritis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Musculoskeletal chest pain † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Spinal pain † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Metastatic pain † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Tumour pain † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	3	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Uterine leiomyoma † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Nervous system disorders
Cerebral haemorrhage † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cerebrovascular accident † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Embolic stroke † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Seizure † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Syncope † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Brain injury † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Cerebral cyst † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Convulsion † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Embolic stroke † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Facial nerve disorder † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Headache † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Ischaemic stroke † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Nervous system disorder † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Partial seizures † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Presyncope † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Psychiatric disorders
Anxiety † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Confusional state † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Delusion † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Depression † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Insomnia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Suicide attempt † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Renal and urinary disorders
Renal failure † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	1/271 (0.37%)	2	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Renal failure acute † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Renal impairment † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	4/271 (1.48%)	4	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Hypoxia † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	1/12 (8.33%)	1	0/28 (0.00%)	0
Interstitial lung disease † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	1/28 (3.57%)	1
Pleural effusion † 1	2/201 (1.00%)	3	1/31 (3.23%)	1	3/271 (1.11%)	3	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pneumonia aspiration † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pneumonitis † 1	3/201 (1.49%)	3	0/31 (0.00%)	0	3/271 (1.11%)	3	2/60 (3.33%)	2	0/12 (0.00%)	0	2/28 (7.14%)	2
Pneumothorax spontaneous † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pulmonary embolism † 1	3/201 (1.49%)	3	0/31 (0.00%)	0	10/271 (3.69%)	13	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Respiratory failure † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pulmonary artery thrombosis † 1	0/201 (0.00%)	0	1/31 (3.23%)	1	0/271 (0.00%)	0	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pneumothorax † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	2/271 (0.74%)	2	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Pulmonary granuloma † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Skin and subcutaneous tissue disorders
Skin toxicity † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Embolism † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Peripheral artery thrombosis † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	AZD9291 80mg Extension		Dose Escalation		Dose Expansion		First Line		80mg Tablet		Japan Cytology
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	191/201 (95.02%)		31/31 (100.00%)		265/271 (97.79%)		60/60 (100.00%)		12/12 (100.00%)		24/28 (85.71%)
Blood and lymphatic system disorders
Anaemia † 1	18/201 (8.96%)	22	6/31 (19.35%)	7	36/271 (13.28%)	49	9/60 (15.00%)	10	0/12 (0.00%)	0	5/28 (17.86%)	5
Leukopenia † 1	9/201 (4.48%)	9	1/31 (3.23%)	1	10/271 (3.69%)	16	4/60 (6.67%)	6	0/12 (0.00%)	0	3/28 (10.71%)	6
Lymphopenia † 1	5/201 (2.49%)	5	1/31 (3.23%)	1	6/271 (2.21%)	8	1/60 (1.67%)	1	0/12 (0.00%)	0	2/28 (7.14%)	2
Neutropenia † 1	7/201 (3.48%)	7	4/31 (12.90%)	8	12/271 (4.43%)	12	3/60 (5.00%)	5	0/12 (0.00%)	0	4/28 (14.29%)	6
Thrombocytopenia † 1	10/201 (4.98%)	10	2/31 (6.45%)	2	20/271 (7.38%)	25	7/60 (11.67%)	9	1/12 (8.33%)	1	2/28 (7.14%)	2
Eye disorders
Dry eye † 1	12/201 (5.97%)	14	3/31 (9.68%)	3	20/271 (7.38%)	21	7/60 (11.67%)	7	0/12 (0.00%)	0	1/28 (3.57%)	1
Blepharitis † 1	2/201 (1.00%)	2	2/31 (6.45%)	2	5/271 (1.85%)	5	3/60 (5.00%)	3	0/12 (0.00%)	0	0/28 (0.00%)	0
Conjunctival haemorrhage † 1	2/201 (1.00%)	2	2/31 (6.45%)	2	3/271 (1.11%)	3	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Vision blurred † 1	4/201 (1.99%)	4	2/31 (6.45%)	3	3/271 (1.11%)	3	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Gastrointestinal disorders
Abdominal pain upper † 1	12/201 (5.97%)	13	2/31 (6.45%)	3	19/271 (7.01%)	26	8/60 (13.33%)	9	0/12 (0.00%)	0	0/28 (0.00%)	0
Constipation † 1	30/201 (14.93%)	31	3/31 (9.68%)	4	60/271 (22.14%)	65	9/60 (15.00%)	11	1/12 (8.33%)	1	2/28 (7.14%)	2
Diarrhoea † 1	93/201 (46.27%)	147	19/31 (61.29%)	38	144/271 (53.14%)	219	41/60 (68.33%)	62	5/12 (41.67%)	6	9/28 (32.14%)	9
Dry mouth † 1	13/201 (6.47%)	13	1/31 (3.23%)	1	17/271 (6.27%)	18	4/60 (6.67%)	4	0/12 (0.00%)	0	1/28 (3.57%)	1
Nausea † 1	34/201 (16.92%)	45	8/31 (25.81%)	9	72/271 (26.57%)	96	15/60 (25.00%)	18	5/12 (41.67%)	5	3/28 (10.71%)	3
Stomatitis † 1	27/201 (13.43%)	28	8/31 (25.81%)	14	50/271 (18.45%)	63	23/60 (38.33%)	36	1/12 (8.33%)	1	5/28 (17.86%)	5
Vomiting † 1	23/201 (11.44%)	31	7/31 (22.58%)	10	48/271 (17.71%)	73	9/60 (15.00%)	13	1/12 (8.33%)	1	1/28 (3.57%)	1
Abdominal pain † 1	10/201 (4.98%)	10	3/31 (9.68%)	3	25/271 (9.23%)	27	4/60 (6.67%)	4	0/12 (0.00%)	0	0/28 (0.00%)	0
Dyspepsia † 1	8/201 (3.98%)	8	4/31 (12.90%)	4	16/271 (5.90%)	18	4/60 (6.67%)	4	1/12 (8.33%)	1	0/28 (0.00%)	0
Gastritis † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	3/271 (1.11%)	3	4/60 (6.67%)	4	0/12 (0.00%)	0	0/28 (0.00%)	0
Gastrooesophageal reflux disease † 1	5/201 (2.49%)	5	0/31 (0.00%)	0	11/271 (4.06%)	11	5/60 (8.33%)	5	2/12 (16.67%)	2	0/28 (0.00%)	0
Mouth ulceration † 1	3/201 (1.49%)	3	0/31 (0.00%)	0	4/271 (1.48%)	4	8/60 (13.33%)	10	0/12 (0.00%)	0	0/28 (0.00%)	0
Abdominal distension † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	13/271 (4.80%)	13	3/60 (5.00%)	3	2/12 (16.67%)	2	0/28 (0.00%)	0
General disorders
Asthenia † 1	19/201 (9.45%)	34	3/31 (9.68%)	3	25/271 (9.23%)	36	2/60 (3.33%)	2	1/12 (8.33%)	1	0/28 (0.00%)	0
Fatigue † 1	24/201 (11.94%)	27	5/31 (16.13%)	6	64/271 (23.62%)	68	15/60 (25.00%)	16	2/12 (16.67%)	4	0/28 (0.00%)	0
Oedema peripheral † 1	15/201 (7.46%)	17	0/31 (0.00%)	0	20/271 (7.38%)	22	2/60 (3.33%)	3	2/12 (16.67%)	4	0/28 (0.00%)	0
Pyrexia † 1	12/201 (5.97%)	13	1/31 (3.23%)	1	27/271 (9.96%)	28	5/60 (8.33%)	5	1/12 (8.33%)	1	1/28 (3.57%)	1
Influenza like illness † 1	3/201 (1.49%)	3	0/31 (0.00%)	0	8/271 (2.95%)	10	5/60 (8.33%)	5	0/12 (0.00%)	0	0/28 (0.00%)	0
Mucosal inflammation † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	16/271 (5.90%)	17	7/60 (11.67%)	7	0/12 (0.00%)	0	0/28 (0.00%)	0
Face oedema † 1	1/201 (0.50%)	1	2/31 (6.45%)	2	3/271 (1.11%)	3	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Non-cardiac chest pain † 1	5/201 (2.49%)	5	0/31 (0.00%)	0	4/271 (1.48%)	4	1/60 (1.67%)	1	2/12 (16.67%)	3	0/28 (0.00%)	0
Infections and infestations
Nasopharyngitis † 1	14/201 (6.97%)	16	6/31 (19.35%)	10	21/271 (7.75%)	26	2/60 (3.33%)	3	1/12 (8.33%)	1	2/28 (7.14%)	2
Paronychia † 1	40/201 (19.90%)	48	8/31 (25.81%)	11	64/271 (23.62%)	75	23/60 (38.33%)	23	2/12 (16.67%)	3	8/28 (28.57%)	8
Upper respiratory tract infection † 1	18/201 (8.96%)	20	6/31 (19.35%)	15	27/271 (9.96%)	29	11/60 (18.33%)	15	4/12 (33.33%)	4	2/28 (7.14%)	2
Conjunctivitis † 1	6/201 (2.99%)	6	1/31 (3.23%)	1	5/271 (1.85%)	6	8/60 (13.33%)	8	0/12 (0.00%)	0	0/28 (0.00%)	0
Folliculitis † 1	3/201 (1.49%)	3	1/31 (3.23%)	1	14/271 (5.17%)	15	3/60 (5.00%)	3	0/12 (0.00%)	0	0/28 (0.00%)	0
Oral herpes † 1	2/201 (1.00%)	2	2/31 (6.45%)	2	2/271 (0.74%)	2	0/60 (0.00%)	0	1/12 (8.33%)	1	2/28 (7.14%)	2
Pharyngitis † 1	7/201 (3.48%)	7	0/31 (0.00%)	0	7/271 (2.58%)	7	1/60 (1.67%)	1	0/12 (0.00%)	0	2/28 (7.14%)	2
Urinary tract infection † 1	10/201 (4.98%)	10	1/31 (3.23%)	1	19/271 (7.01%)	26	2/60 (3.33%)	3	1/12 (8.33%)	2	1/28 (3.57%)	1
Bronchitis † 1	7/201 (3.48%)	7	2/31 (6.45%)	2	6/271 (2.21%)	6	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Rash pustular † 1	5/201 (2.49%)	5	1/31 (3.23%)	4	4/271 (1.48%)	4	1/60 (1.67%)	1	2/12 (16.67%)	2	0/28 (0.00%)	0
Sinusitis † 1	3/201 (1.49%)	3	1/31 (3.23%)	1	7/271 (2.58%)	7	0/60 (0.00%)	0	2/12 (16.67%)	4	0/28 (0.00%)	0
Injury, poisoning and procedural complications
Traumatic fracture † 1	3/201 (1.49%)	3	2/31 (6.45%)	2	5/271 (1.85%)	5	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	12/201 (5.97%)	13	3/31 (9.68%)	3	16/271 (5.90%)	23	6/60 (10.00%)	10	0/12 (0.00%)	0	0/28 (0.00%)	0
Aspartate aminotransferase increased † 1	14/201 (6.97%)	18	2/31 (6.45%)	2	19/271 (7.01%)	27	7/60 (11.67%)	11	0/12 (0.00%)	0	0/28 (0.00%)	0
Platelet count decreased † 1	26/201 (12.94%)	38	1/31 (3.23%)	1	24/271 (8.86%)	31	8/60 (13.33%)	12	0/12 (0.00%)	0	3/28 (10.71%)	4
White blood cell count decreased † 1	15/201 (7.46%)	19	3/31 (9.68%)	4	8/271 (2.95%)	20	10/60 (16.67%)	17	0/12 (0.00%)	0	5/28 (17.86%)	7
Electrocardiogram QT prolonged † 1	6/201 (2.99%)	6	0/31 (0.00%)	0	9/271 (3.32%)	10	5/60 (8.33%)	5	1/12 (8.33%)	1	3/28 (10.71%)	3
Lymphocyte count decreased † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	7/271 (2.58%)	8	3/60 (5.00%)	3	0/12 (0.00%)	0	2/28 (7.14%)	6
Neutrophil count decreased † 1	10/201 (4.98%)	10	3/31 (9.68%)	6	16/271 (5.90%)	38	5/60 (8.33%)	5	0/12 (0.00%)	0	6/28 (21.43%)	8
Weight decreased † 1	6/201 (2.99%)	6	2/31 (6.45%)	2	19/271 (7.01%)	19	13/60 (21.67%)	13	1/12 (8.33%)	1	1/28 (3.57%)	1
Renal function test abnormal † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	0/271 (0.00%)	0	0/60 (0.00%)	0	2/12 (16.67%)	2	0/28 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	36/201 (17.91%)	41	12/31 (38.71%)	18	69/271 (25.46%)	80	15/60 (25.00%)	15	3/12 (25.00%)	4	1/28 (3.57%)	1
Hyperkalaemia † 1	2/201 (1.00%)	2	1/31 (3.23%)	1	8/271 (2.95%)	10	1/60 (1.67%)	1	1/12 (8.33%)	3	2/28 (7.14%)	2
Dehydration † 1	4/201 (1.99%)	4	2/31 (6.45%)	2	7/271 (2.58%)	7	2/60 (3.33%)	2	1/12 (8.33%)	1	0/28 (0.00%)	0
Hypocalcaemia † 1	6/201 (2.99%)	6	3/31 (9.68%)	3	8/271 (2.95%)	8	3/60 (5.00%)	3	0/12 (0.00%)	0	0/28 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	16/201 (7.96%)	18	4/31 (12.90%)	4	26/271 (9.59%)	33	2/60 (3.33%)	2	2/12 (16.67%)	2	1/28 (3.57%)	1
Back pain † 1	27/201 (13.43%)	29	3/31 (9.68%)	6	27/271 (9.96%)	30	6/60 (10.00%)	7	2/12 (16.67%)	2	0/28 (0.00%)	0
Muscle spasms † 1	13/201 (6.47%)	14	3/31 (9.68%)	4	24/271 (8.86%)	27	8/60 (13.33%)	8	2/12 (16.67%)	2	0/28 (0.00%)	0
Musculoskeletal pain † 1	15/201 (7.46%)	16	2/31 (6.45%)	2	20/271 (7.38%)	20	0/60 (0.00%)	0	2/12 (16.67%)	2	2/28 (7.14%)	2
Musculoskeletal chest pain † 1	7/201 (3.48%)	7	0/31 (0.00%)	0	19/271 (7.01%)	20	6/60 (10.00%)	6	1/12 (8.33%)	1	0/28 (0.00%)	0
Myalgia † 1	9/201 (4.48%)	9	1/31 (3.23%)	1	13/271 (4.80%)	13	4/60 (6.67%)	4	3/12 (25.00%)	3	0/28 (0.00%)	0
Pain in extremity † 1	10/201 (4.98%)	10	0/31 (0.00%)	0	19/271 (7.01%)	22	2/60 (3.33%)	2	4/12 (33.33%)	7	0/28 (0.00%)	0
Muscle atrophy † 1	0/201 (0.00%)	0	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	2/12 (16.67%)	2	0/28 (0.00%)	0
Muscular weakness † 1	3/201 (1.49%)	3	2/31 (6.45%)	2	4/271 (1.48%)	4	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Nervous system disorders
Headache † 1	22/201 (10.95%)	22	4/31 (12.90%)	7	30/271 (11.07%)	34	5/60 (8.33%)	8	1/12 (8.33%)	3	0/28 (0.00%)	0
Dizziness † 1	9/201 (4.48%)	9	1/31 (3.23%)	1	25/271 (9.23%)	29	5/60 (8.33%)	5	2/12 (16.67%)	2	0/28 (0.00%)	0
Dysgeusia † 1	4/201 (1.99%)	4	3/31 (9.68%)	3	15/271 (5.54%)	16	10/60 (16.67%)	12	0/12 (0.00%)	0	1/28 (3.57%)	1
Paraesthesia † 1	1/201 (0.50%)	1	3/31 (9.68%)	3	7/271 (2.58%)	7	3/60 (5.00%)	3	0/12 (0.00%)	0	0/28 (0.00%)	0
Peripheral sensory neuropathy † 1	1/201 (0.50%)	1	2/31 (6.45%)	2	7/271 (2.58%)	7	2/60 (3.33%)	2	0/12 (0.00%)	0	0/28 (0.00%)	0
Psychiatric disorders
Insomnia † 1	19/201 (9.45%)	21	1/31 (3.23%)	1	27/271 (9.96%)	28	7/60 (11.67%)	10	2/12 (16.67%)	2	0/28 (0.00%)	0
Anxiety † 1	4/201 (1.99%)	4	0/31 (0.00%)	0	11/271 (4.06%)	11	1/60 (1.67%)	1	2/12 (16.67%)	2	0/28 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	32/201 (15.92%)	36	4/31 (12.90%)	4	55/271 (20.30%)	64	9/60 (15.00%)	11	2/12 (16.67%)	2	0/28 (0.00%)	0
Dyspnoea † 1	18/201 (8.96%)	19	2/31 (6.45%)	3	37/271 (13.65%)	43	2/60 (3.33%)	2	4/12 (33.33%)	5	0/28 (0.00%)	0
Epistaxis † 1	6/201 (2.99%)	6	1/31 (3.23%)	1	13/271 (4.80%)	14	9/60 (15.00%)	11	1/12 (8.33%)	1	0/28 (0.00%)	0
Haemoptysis † 1	8/201 (3.98%)	8	0/31 (0.00%)	0	6/271 (2.21%)	6	4/60 (6.67%)	4	1/12 (8.33%)	2	0/28 (0.00%)	0
Rhinorrhoea † 1	5/201 (2.49%)	5	2/31 (6.45%)	2	20/271 (7.38%)	20	3/60 (5.00%)	4	1/12 (8.33%)	1	0/28 (0.00%)	0
Dysphonia † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	13/271 (4.80%)	13	0/60 (0.00%)	0	2/12 (16.67%)	2	0/28 (0.00%)	0
Hypoxia † 1	5/201 (2.49%)	5	0/31 (0.00%)	0	1/271 (0.37%)	1	0/60 (0.00%)	0	2/12 (16.67%)	4	0/28 (0.00%)	0
Oropharyngeal pain † 1	4/201 (1.99%)	4	4/31 (12.90%)	4	11/271 (4.06%)	11	3/60 (5.00%)	3	3/12 (25.00%)	3	0/28 (0.00%)	0
Pulmonary embolism † 1	7/201 (3.48%)	7	3/31 (9.68%)	4	17/271 (6.27%)	17	4/60 (6.67%)	4	1/12 (8.33%)	1	0/28 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis acneiform † 1	12/201 (5.97%)	13	3/31 (9.68%)	3	32/271 (11.81%)	39	16/60 (26.67%)	17	0/12 (0.00%)	0	2/28 (7.14%)	2
Dry skin † 1	43/201 (21.39%)	45	8/31 (25.81%)	8	62/271 (22.88%)	73	24/60 (40.00%)	29	4/12 (33.33%)	4	8/28 (28.57%)	8
Pruritus † 1	25/201 (12.44%)	29	8/31 (25.81%)	9	56/271 (20.66%)	61	14/60 (23.33%)	15	3/12 (25.00%)	4	3/28 (10.71%)	3
Rash † 1	49/201 (24.38%)	58	11/31 (35.48%)	17	75/271 (27.68%)	101	20/60 (33.33%)	25	2/12 (16.67%)	2	3/28 (10.71%)	3
Skin fissures † 1	12/201 (5.97%)	12	4/31 (12.90%)	4	30/271 (11.07%)	31	9/60 (15.00%)	9	1/12 (8.33%)	1	1/28 (3.57%)	2
Acne † 1	2/201 (1.00%)	2	0/31 (0.00%)	0	11/271 (4.06%)	12	4/60 (6.67%)	4	0/12 (0.00%)	0	1/28 (3.57%)	1
Alopecia † 1	7/201 (3.48%)	7	0/31 (0.00%)	0	10/271 (3.69%)	11	6/60 (10.00%)	6	2/12 (16.67%)	2	0/28 (0.00%)	0
Eczema † 1	2/201 (1.00%)	2	1/31 (3.23%)	1	4/271 (1.48%)	4	4/60 (6.67%)	4	0/12 (0.00%)	0	2/28 (7.14%)	2
Erythema † 1	7/201 (3.48%)	7	1/31 (3.23%)	1	9/271 (3.32%)	9	1/60 (1.67%)	1	0/12 (0.00%)	0	2/28 (7.14%)	2
Palmar-plantar erythrodysaesthesia syndrome † 1	1/201 (0.50%)	1	0/31 (0.00%)	0	0/271 (0.00%)	0	4/60 (6.67%)	4	0/12 (0.00%)	0	0/28 (0.00%)	0
Rash maculo-papular † 1	9/201 (4.48%)	9	1/31 (3.23%)	4	11/271 (4.06%)	15	5/60 (8.33%)	6	1/12 (8.33%)	2	1/28 (3.57%)	1
Skin exfoliation † 1	2/201 (1.00%)	2	2/31 (6.45%)	2	14/271 (5.17%)	15	3/60 (5.00%)	3	0/12 (0.00%)	0	1/28 (3.57%)	1
Nail discolouration † 1	4/201 (1.99%)	4	2/31 (6.45%)	2	0/271 (0.00%)	0	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Nail disorder † 1	4/201 (1.99%)	4	3/31 (9.68%)	3	10/271 (3.69%)	10	1/60 (1.67%)	1	0/12 (0.00%)	0	0/28 (0.00%)	0
Rash erythematous † 1	0/201 (0.00%)	0	2/31 (6.45%)	2	3/271 (1.11%)	3	0/60 (0.00%)	0	0/12 (0.00%)	0	0/28 (0.00%)	0
Vascular disorders
Hypertension † 1	3/201 (1.49%)	3	1/31 (3.23%)	1	7/271 (2.58%)	8	4/60 (6.67%)	5	2/12 (16.67%)	2	0/28 (0.00%)	0
Hypotension † 1	4/201 (1.99%)	4	1/31 (3.23%)	1	3/271 (1.11%)	3	0/60 (0.00%)	0	2/12 (16.67%)	2	0/28 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

All 6 cohorts are still on-going. Data cut-off on 1st May 2015 was for primary analyses in main cohorts of dose escalation, dose expansion, extension. AEs presented for all cohorts.

More Information

Certain Agreements

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

There IS 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.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review, should the submission for publication be delayed in order to file patent application. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

• Name/Title: Senior Medical Director, Tagrisso
• Organization: AstraZeneca
• EMail: ClinicalTrialTransparency@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.

Ahn MJ, Han JY, Kim DW, Cho BC, Kang JH, Kim SW, Yang JC, Mitsudomi T, Lee JS. Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies. Cancer Res Treat. 2020 Jan;52(1):284-291. doi: 10.4143/crt.2019.200. Epub 2019 Jul 23.

Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.

Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Janne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018 Nov 1;4(11):1527-1534. doi: 10.1001/jamaoncol.2018.2969.

Kiura K, Yoh K, Katakami N, Nogami N, Kasahara K, Takahashi T, Okamoto I, Cantarini M, Hodge R, Uchida H. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci. 2018 Apr;109(4):1177-1184. doi: 10.1111/cas.13511. Epub 2018 Feb 27.

Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.

Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Janne PA. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Mar 20;36(9):841-849. doi: 10.1200/JCO.2017.74.7576. Epub 2017 Aug 25.

Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Janne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol. 2017 Oct;12(10):1588-1594. doi: 10.1016/j.jtho.2017.07.011. Epub 2017 Jul 24.

Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Janne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.

Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne PA, Cross D. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res. 2016 Oct 15;22(20):5130-5140. doi: 10.1158/1078-0432.CCR-16-0399. Epub 2016 Jul 19.

Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.

Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015 Dec;90(3):509-15. doi: 10.1016/j.lungcan.2015.10.004. Epub 2015 Oct 9.

Kim TM, Song A, Kim DW, Kim S, Ahn YO, Keam B, Jeon YK, Lee SH, Chung DH, Heo DS. Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44. doi: 10.1097/JTO.0000000000000688.

Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain. JAMA Oncol. 2015 Oct;1(7):982-4. doi: 10.1001/jamaoncol.2015.1066. No abstract available.

Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01802632
• Other Study ID Numbers: D5160C00001; 2012-004628-39 ( EudraCT Number )
• First Submitted: February 25, 2013
• First Posted: March 1, 2013
• Results First Submitted: April 29, 2016
• Results First Posted: October 6, 2016
• Last Update Posted: January 18, 2024