A Global Study to Assess the Effects of MEDI4736 (Durvalu... | NCT02087423

NCT02087423

ID	Type	Description	Link
2013-005427-16	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
MEDI4736	Experimental	see below	Drug: MEDI4736

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MEDI4736	Drug	MEDI4736 (durvalumab) by intravenous infusion every two weeks. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier. Patients who achieve CR, PR or SD through the end of the initial 12-month treatment period can restart treatment with MEDI4736 (durvalumab) when they eventually do progress. This retreatment period can continue for as long as the investigator considers to patient to be receiving clinical benefit.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	Patients commenced treatment with durvalumab on Day 1 and continued on a Q2W schedule for a maximum of 12 months. Tumor assessments using computed tomography / magnetic resonance imaging were performed every 8 weeks. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) measurements as given by the Independent Central Review (ICR) were used to derive the primary variable of ORR .	Responses recorded during initial 12 month treatment period (up to primary analysis DCO)

Secondary Outcomes

Measure	Description	Time Frame
Time to Response (TTR)	TTR (per RECIST 1.1 as assessed by the ICR) is defined as the time from the date of first dose until the date of first documented response (which is subsequently confirmed). TTR was only analyzed for Cohort 2.	Responses recorded during initial 12 month treatment period (up to primary analysis DCO)

Eligibility Module

Name	Affiliation	Role
Phillip Dennis, MD, PhD	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Goodyear	Arizona	85338	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33319498	Derived	Gavrilov S, Zhudenkov K, Helmlinger G, Dunyak J, Peskov K, Aksenov S. Longitudinal Tumor Size and Neutrophil-to-Lymphocyte Ratio Are Prognostic Biomarkers for Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Durvalumab. CPT Pharmacometrics Syst Pharmacol. 2021 Jan;10(1):67-74. doi: 10.1002/psp4.12578. Epub 2020 Dec 21.
32816849

Label	URL
d4191c00003 revised csp 4 Redacted	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1 (EGFR/ALK+)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Cohort 1 (EGFR/ALK+)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
BG001	Cohort 2	Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
BG002	Cohort 3 (TC >= 90%)	Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

age groups of <=18, between 18 and 65, >=65,

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Median

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00061.0± 11.45 BG00162.0± 9.35 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00070 BG001103 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG00044 BG001212 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0006 BG00119 BG002

Weight

Median

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00059± 14.15 BG00168± 14.52 BG002

Weight group

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<70 kg	BG00081 BG001146 BG002

WHO performance status

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
(0) Normal activity	BG00045 BG00186 BG002

Primary tumor location

Lung

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG000111 BG001265 BG002

Histology type

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Squamous	BG0001 BG00155 BG002

AJCC staging at initial diagnosis

Per tumor, node, metastasis (TNM) staging system as specified by American Joint Committee on Cancer (AJCC). The staging is determined by a number of different parameters and the higher the staging the worse the prognosis for survival.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Stage IA	BG0002 BG001

Best response to previous therapy

based on the last therapy received prior to entering the study

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
complete response	BG0000 BG0011 BG002

Time from informed consent to first dose

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=14 days	BG00021 BG00168 BG002

Overall disease classification

either patient has any metastatic site of disease or has only locally advanced sites of disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Metastatic	BG000102 BG001245

PD-L1 expression level

% of tumor cells with membrane staining for PD-L1

Number

Number of patients (per PD-L1 category)

Title

Denominators

Categories

Positive (>=25%)

Title	Measurements
	BG00077 BG001149 BG002

Smoking history

Patients who checked options Cigarettes, Cigarillos, Cigars, Pipe Tobacco, or Tobacco for Smoking are considered smokers.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Non-smoker	BG00065 BG00139

Number of regimens of previous anti-cancer therapy

Median

Standard Deviation

Number of regimens

Title

Denominators

Categories

Title	Measurements
	BG0003± 2.00 BG0013± 1.38 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR)

Patients commenced treatment with durvalumab on Day 1 and continued on a Q2W schedule for a maximum of 12 months. Tumor assessments using computed tomography / magnetic resonance imaging were performed every 8 weeks. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) measurements as given by the Independent Central Review (ICR) were used to derive the primary variable of ORR .

The "Full analysis set [FAS] - evaluable for response per ICR" set, included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

Posted

Number

95% Confidence Interval

% of patients evaluable for response

Responses recorded during initial 12 month treatment period (up to primary analysis DCO)

ID	Title	Description
OG000	Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown. patients with PD-L1 TC>=90% are included in this group.
OG001	Cohort 1 (EGFR/ALK+) PD-L1+ (<25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
OG002	Cohort 2 PD-L1+ (>=25%)	Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown. Patients with PD-L1 TC>=90% are included within the PD-L1 high (TC>=25%) group.
OG003	Cohort 2 PD-L1+ (<25%)	Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
OG004	Cohort 3 (TC>=90%)	Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC>=90%).

Units	Counts
Participants	OG00074 OG00128 OG002146 OG003

Title

Denominators

Categories

Title	Measurements
	OG00012.2(5.7 to 21.8) OG0013.6(0.1 to 18.3) OG00216.4(10.8 to 23.5) OG003

Secondary

Time to Response (TTR)

TTR (per RECIST 1.1 as assessed by the ICR) is defined as the time from the date of first dose until the date of first documented response (which is subsequently confirmed). TTR was only analyzed for Cohort 2.

The "FAS - evaluable for response per ICR" set for Cohort 2, included all treated patients in Cohort 2 who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

Posted

Median

Full Range

Months

Responses recorded during initial 12 month treatment period (up to primary analysis DCO)

ID	Title	Description
OG000	Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown. patients with PD-L1 TC>=90% are included in this group.
OG001	Cohort 1 (EGFR/ALK+) PD-L1+ (<25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
OG002

Secondary

Duration of Response (DoR)

DoR (per RECIST 1.1 as assessed by the ICR) was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). DoR was only analyzed for Cohort 2. Cohort 2: Median DoR was 12.3 months in the PD-L1 high (TC>=25%) group at DCO (Q3 was NR). Of the 7 evaluable patients, the median DoR was not reached in the PD-L1 low/neg group (TC <25%); therefore the DoR "number of participants analyzed" field has been entered as "0" and the DoR results field has been left blank.

The "FAS - evaluable for response per ICR" set for Cohort 2, included all treated patients in Cohort 2 who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

Posted

Median

Inter-Quartile Range

Months

Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO)

ID	Title	Description
OG000	Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown. patients with PD-L1 TC>=90% are included in this group.
OG001	Cohort 1 (EGFR/ALK+) PD-L1+ (<25%)

Secondary

Overall Survival (OS)

OS was defined as the time from the date of first dose until death due to any cause (ie, date of death or censoring - date of first dose + 1). Results are reported as median OS, calculated using the Kaplan-Meier methodology.

The FAS included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

Posted

Median

95% Confidence Interval

Months

From date of first treatment until final DCO (up to approximately 3 years 8 months)

ID	Title	Description
OG000	Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown. patients with PD-L1 TC>=90% are included in this group.
OG001	Cohort 1 (EGFR/ALK+) PD-L1+ (<25%)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
OG002	Cohort 2 PD-L1+ (>=25%)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1 (EGFR/ALK+)	Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.	70	111	18	111	96	111
EG001	Cohort 2	Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.	217	265	77	265	233	265
EG002	Cohort 3 (TC >=90%)	Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).	41	68	24	68	60	68

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0017 events3 affected265 at risk EG0022 events2 affected68 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0013 events2 affected265 at risk EG0021 events1 affected68 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pericardial effusion	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Hypopituitarism	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Subileus	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0013 events1 affected265 at risk EG0021 events1 affected68 at risk
Sudden death	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Hepatic atrophy	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Meningitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Ophthalmic herpes zoster	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0019 events8 affected265 at risk EG0021 events1 affected68 at risk
Sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0013 events3 affected265 at risk EG0020 events0 affected68 at risk
Septic shock	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Seizure	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Somnolence	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0012 events2 affected265 at risk EG0022 events2 affected68 at risk
Vena cava thrombosis	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Bradycardia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events2 affected265 at risk EG0021 events1 affected68 at risk
Diabetes insipidus	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Hypothyroidism	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0013 events3 affected265 at risk EG0021 events1 affected68 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events2 affected265 at risk EG0021 events1 affected68 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Oesophageal rupture	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Asthenia	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0013 events3 affected265 at risk EG0021 events1 affected68 at risk
General physical health deterioration	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events2 affected265 at risk EG0020 events0 affected68 at risk
Malaise	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0022 events2 affected68 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Bronchitis bacterial	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Campylobacter gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Cellulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Central nervous system infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Device related infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Diverticulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events2 affected265 at risk EG0020 events0 affected68 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Lung abscess	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events1 affected265 at risk EG0020 events0 affected68 at risk
Lung infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pneumococcal sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0014 events2 affected265 at risk EG0020 events0 affected68 at risk
Staphylococcal infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Streptococcal abscess	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Hepatic enzyme increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Transaminases increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Urine output decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Weight decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Memory impairment	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Spinal cord compression	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Mental status changes	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Nephritis	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG0017 events7 affected265 at risk EG0020 events0 affected68 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected111 at risk EG0011 events1 affected265 at risk EG0021 events1 affected68 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0022 events1 affected68 at risk
Organising pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0015 events5 affected265 at risk EG0021 events1 affected68 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0014 events4 affected265 at risk EG0020 events0 affected68 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0010 events0 affected265 at risk EG0020 events0 affected68 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0012 events2 affected265 at risk EG0020 events0 affected68 at risk
Hypertensive crisis	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0010 events0 affected265 at risk EG0021 events1 affected68 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG0011 events1 affected265 at risk EG0020 events0 affected68 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG00152 events43 affected265 at risk EG0028 events8 affected68 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG00012 events11 affected111 at risk EG00118 events17 affected265 at risk EG0028 events7 affected68 at risk
Hypothyroidism	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG00014 events11 affected111 at risk EG00124 events19 affected265 at risk EG0029 events8 affected68 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0006 events5 affected111 at risk EG00110 events10 affected265 at risk EG0026 events4 affected68 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0008 events7 affected111 at risk EG00112 events12 affected265 at risk EG0021 events1 affected68 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00015 events14 affected111 at risk EG00145 events37 affected265 at risk EG00219 events16 affected68 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00014 events11 affected111 at risk EG00153 events39 affected265 at risk EG00210 events9 affected68 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00016 events14 affected111 at risk EG00157 events46 affected265 at risk EG00215 events12 affected68 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00015 events13 affected111 at risk EG00136 events27 affected265 at risk EG00213 events10 affected68 at risk
Asthenia	General disorders	MedDRA 20.0	Systematic Assessment	EG00015 events14 affected111 at risk EG00176 events53 affected265 at risk EG0024 events4 affected68 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG00016 events15 affected111 at risk EG00180 events69 affected265 at risk EG00231 events20 affected68 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0004 events3 affected111 at risk EG00115 events10 affected265 at risk EG0025 events4 affected68 at risk
Oedema peripheral	General disorders	MedDRA 20.0	Systematic Assessment	EG0008 events7 affected111 at risk EG00125 events25 affected265 at risk EG00213 events9 affected68 at risk
Pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected111 at risk EG0018 events8 affected265 at risk EG0024 events4 affected68 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG00014 events12 affected111 at risk EG00181 events53 affected265 at risk EG00216 events12 affected68 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected111 at risk EG0014 events4 affected265 at risk EG0025 events4 affected68 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0009 events6 affected111 at risk EG0018 events8 affected265 at risk EG0026 events6 affected68 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected111 at risk EG00119 events15 affected265 at risk EG0024 events3 affected68 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0006 events5 affected111 at risk EG00113 events12 affected265 at risk EG00218 events11 affected68 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected111 at risk EG00113 events11 affected265 at risk EG0025 events5 affected68 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG00114 events12 affected265 at risk EG0025 events5 affected68 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected111 at risk EG00114 events14 affected265 at risk EG0022 events2 affected68 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected111 at risk EG00115 events15 affected265 at risk EG0020 events0 affected68 at risk
Weight decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG00122 events22 affected265 at risk EG00213 events13 affected68 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG00015 events15 affected111 at risk EG00177 events71 affected265 at risk EG00212 events12 affected68 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected111 at risk EG00120 events14 affected265 at risk EG0025 events4 affected68 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0007 events7 affected111 at risk EG00125 events21 affected265 at risk EG0026 events5 affected68 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG00011 events11 affected111 at risk EG00124 events23 affected265 at risk EG00210 events8 affected68 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected111 at risk EG00121 events16 affected265 at risk EG0024 events3 affected68 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG0018 events8 affected265 at risk EG0027 events7 affected68 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected111 at risk EG00121 events18 affected265 at risk EG0022 events2 affected68 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0006 events6 affected111 at risk EG00118 events12 affected265 at risk EG0026 events4 affected68 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG00015 events13 affected111 at risk EG00132 events26 affected265 at risk EG0026 events6 affected68 at risk
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected111 at risk EG00116 events16 affected265 at risk EG0022 events2 affected68 at risk
Insomnia	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG00012 events10 affected111 at risk EG00119 events16 affected265 at risk EG0025 events5 affected68 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG00032 events26 affected111 at risk EG00167 events56 affected265 at risk EG00216 events13 affected68 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected111 at risk EG00115 events14 affected265 at risk EG0021 events1 affected68 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG00014 events13 affected111 at risk EG00146 events43 affected265 at risk EG00210 events7 affected68 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected111 at risk EG00120 events14 affected265 at risk EG0026 events4 affected68 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected111 at risk EG00123 events20 affected265 at risk EG0024 events4 affected68 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG00011 events9 affected111 at risk EG00139 events27 affected265 at risk EG00214 events13 affected68 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0009 events7 affected111 at risk EG00120 events19 affected265 at risk EG0028 events8 affected68 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D009362	Neoplasm Metastasis

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms