Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Plac... | NCT03322540

NCT03322540

ID	Type	Description	Link
2017-001841-28	EudraCT Number

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + Epacadostat	Experimental	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.	Drug: Pembrolizumab Drug: Epacadostat
Pembrolizumab + Placebo	Active Comparator	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.	Drug: Pembrolizumab Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Drug	Pembrolizumab administered intravenously every 3 weeks.	Pembrolizumab + Epacadostat Pembrolizumab + Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo	ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).	Up to approximately 6 months

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 based on BICR or death due to any cause, whichever occurs first.	Up to approximately 36 months
Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

Eligibility Module

Name	Affiliation	Role
Lance Leopold, MD	Incyte Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pacific Cancer Medical Center, Inc.		Anaheim	California	92801	United States
Innovative Clinical Research Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39054476	Derived	Tokito T, Kolesnik O, Sorensen J, Artac M, Quintela ML, Lee JS, Hussein M, Pless M, Paz-Ares L, Leopold L, Daniel J, Munteanu M, Samkari A, Xu L, Butts C. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab as first-line treatment for metastatic non-small cell lung cancer with high levels of programmed death-ligand 1: a randomized, double-blind phase 2 study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1251. doi: 10.1186/s12885-023-11203-8.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + Epacadostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 4, 2019	Nov 17, 2021

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + Epacadostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
BG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.
BG002	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, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.7± 9.5 BG00166.9± 10.1 BG00265.3± 9.9

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00024 BG00118 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG00025 BG00123 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Not Hispanic Or Latino

Title	Measurements
Hispanic Or Latino	BG0007 BG0014 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) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo

ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).

ITT population consisted of all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 6 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts
Participants	OG00077 OG00177

Title

Denominators

Categories

Title	Measurements
	OG00032.5(22.2 to 44.1) OG00139.0(28.0 to 50.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Stratified Miettinen and Nurminen method	One-sided p-value for testing. H0: difference in % = 0 versus H1: difference in % > 0.	0.8000		Difference in Percentages	-6.5			2-Sided	95	-21.5	8.7			Point estimate was assessed based on Miettinen & Nurminen method stratified by predominant tumor histology (squamous vs non-squamous).		Superiority

Secondary

Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 based on BICR or death due to any cause, whichever occurs first.

ITT population consisted of all randomized participants.

Posted

Median

95% Confidence Interval

months

Up to approximately 36 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts
Participants

Secondary

Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

OS is defined as the time from randomization to death due to any cause.

ITT population consisted of all randomized participants.

Posted

Median

95% Confidence Interval

Months

Up to approximately 36 months

ID	Title	Description
OG000	Pembrolizumab + Epacodostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts
Participants

Secondary

Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first.

DOR included all responders in ITT population. Response duration was calculated from product-limit (Kaplan-Meier) method for censored data.

Posted

Median

Full Range

Months

Up to approximately 36 months

ID	Title	Description
OG000	Pembrolizumab + Epacodostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts

Secondary

Number of Participants With Adverse Events (AEs)

AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Posted

Number

Participants

Up to 37 months

ID	Title	Description
OG000	Pembrolizumab + Epacodostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts
Participants

Secondary

Number of Participants Who Discontinued Study Drug Due to AEs

Posted

Number

Participants

Up to 37 months

ID	Title	Description
OG000	Pembrolizumab + Epacodostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.

Units	Counts
Participants

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	Pembrolizumab + Epacadostat	Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.	23	75	36	75	69	75
EG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.	29	77	35	77	67	77
EG002	Total	Total	52	152	71	152	136	152

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute kidney injury	Renal and urinary disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 23	Systematic Assessment	EG0002 events2 affected75 at risk EG0010 events0 affected77 at risk EG0022 events2 affected152 at risk
Asthenia	General disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0002 events2 affected75 at risk EG0010 events0 affected77 at risk EG0022 events2 affected152 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Autoimmune myocarditis	Cardiac disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Cardiac arrest	Cardiac disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Cholangitis sclerosing	Hepatobiliary disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Colitis	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0002 events1 affected75 at risk EG0010 events0 affected77 at risk EG0022 events1 affected152 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Constipation	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Death	General disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Epilepsy	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Fear of death	Psychiatric disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Gastroenteritis	Infections and infestations	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
General physical health deterioration	General disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected77 at risk EG0022 events2 affected152 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
High-grade B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events2 affected77 at risk EG0022 events2 affected152 at risk
Hypotension	Vascular disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events2 affected77 at risk EG0022 events2 affected152 at risk
Hypothyroidism	Endocrine disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected77 at risk EG0022 events2 affected152 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Ileus	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23	Systematic Assessment	EG0006 events6 affected75 at risk EG0018 events8 affected77 at risk EG00214 events14 affected152 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Pericardial effusion	Cardiac disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Peritonitis	Infections and infestations	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0002 events1 affected75 at risk EG0011 events1 affected77 at risk EG0023 events2 affected152 at risk
Pneumonia	Infections and infestations	MedDRA 23	Systematic Assessment	EG0006 events6 affected75 at risk EG0017 events7 affected77 at risk EG00213 events13 affected152 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0012 events2 affected77 at risk EG0026 events6 affected152 at risk
Polyneuropathy	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Priapism	Reproductive system and breast disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Pseudodiverticular disease	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Pyelonephritis	Infections and infestations	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected77 at risk EG0022 events2 affected152 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Septic shock	Infections and infestations	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Spinal cord compression	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Tumour pseudoprogression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Urinary tract infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected77 at risk EG0021 events1 affected152 at risk
Viral infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected77 at risk EG0021 events1 affected152 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alanine aminotransferase increased	Investigations	MedDRA 23	Systematic Assessment	EG0005 events5 affected75 at risk EG0018 events5 affected77 at risk EG00213 events10 affected152 at risk
Amylase increased	Investigations	MedDRA 23	Systematic Assessment	EG0009 events8 affected75 at risk EG0018 events4 affected77 at risk EG00217 events12 affected152 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 23	Systematic Assessment	EG0008 events7 affected75 at risk EG00112 events10 affected77 at risk EG00220 events17 affected152 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG00022 events17 affected75 at risk EG00112 events10 affected77 at risk EG00234 events27 affected152 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0017 events4 affected77 at risk EG00211 events8 affected152 at risk
Asthenia	General disorders	MedDRA 23	Systematic Assessment	EG0009 events8 affected75 at risk EG0018 events6 affected77 at risk EG00217 events14 affected152 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG00013 events10 affected75 at risk EG00111 events8 affected77 at risk EG00224 events18 affected152 at risk
Blood creatinine increased	Investigations	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0018 events7 affected77 at risk EG00212 events11 affected152 at risk
Chest pain	General disorders	MedDRA 23	Systematic Assessment	EG0005 events5 affected75 at risk EG0017 events6 affected77 at risk EG00212 events11 affected152 at risk
Chills	General disorders	MedDRA 23	Systematic Assessment	EG0005 events4 affected75 at risk EG0012 events1 affected77 at risk EG0027 events5 affected152 at risk
Constipation	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG00023 events20 affected75 at risk EG00121 events18 affected77 at risk EG00244 events38 affected152 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0009 events7 affected75 at risk EG0018 events8 affected77 at risk EG00217 events15 affected152 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG00018 events17 affected75 at risk EG00112 events10 affected77 at risk EG00230 events27 affected152 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG00030 events16 affected75 at risk EG00125 events17 affected77 at risk EG00255 events33 affected152 at risk
Dizziness	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0005 events5 affected75 at risk EG0016 events6 affected77 at risk EG00211 events11 affected152 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 23	Systematic Assessment	EG0005 events5 affected75 at risk EG0014 events4 affected77 at risk EG0029 events9 affected152 at risk
Dysgeusia	Nervous system disorders	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0011 events1 affected77 at risk EG0025 events5 affected152 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG00013 events10 affected75 at risk EG00113 events10 affected77 at risk EG00226 events20 affected152 at risk
Fatigue	General disorders	MedDRA 23	Systematic Assessment	EG00011 events9 affected75 at risk EG00121 events16 affected77 at risk EG00232 events25 affected152 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0006 events6 affected75 at risk EG0017 events7 affected77 at risk EG00213 events13 affected152 at risk
Headache	Nervous system disorders	MedDRA 23	Systematic Assessment	EG00015 events13 affected75 at risk EG0014 events4 affected77 at risk EG00219 events17 affected152 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0007 events6 affected75 at risk EG0012 events2 affected77 at risk EG0029 events8 affected152 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0005 events2 affected75 at risk EG00111 events7 affected77 at risk EG00216 events9 affected152 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 23	Systematic Assessment	EG0008 events8 affected75 at risk EG0016 events6 affected77 at risk EG00214 events14 affected152 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0006 events4 affected75 at risk EG0017 events5 affected77 at risk EG00213 events9 affected152 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23	Systematic Assessment	EG0008 events6 affected75 at risk EG0011 events1 affected77 at risk EG0029 events7 affected152 at risk
Hypotension	Vascular disorders	MedDRA 23	Systematic Assessment	EG0002 events2 affected75 at risk EG0014 events4 affected77 at risk EG0026 events6 affected152 at risk
Hypothyroidism	Endocrine disorders	MedDRA 23	Systematic Assessment	EG00011 events10 affected75 at risk EG0016 events6 affected77 at risk EG00217 events16 affected152 at risk
Insomnia	Psychiatric disorders	MedDRA 23	Systematic Assessment	EG0007 events6 affected75 at risk EG0015 events4 affected77 at risk EG00212 events10 affected152 at risk
Lipase increased	Investigations	MedDRA 23	Systematic Assessment	EG0009 events9 affected75 at risk EG0015 events4 affected77 at risk EG00214 events13 affected152 at risk
Lymphocyte count decreased	Investigations	MedDRA 23	Systematic Assessment	EG0001 events1 affected75 at risk EG0017 events4 affected77 at risk EG0028 events5 affected152 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG0002 events2 affected75 at risk EG0019 events7 affected77 at risk EG00211 events9 affected152 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23	Systematic Assessment	EG0002 events2 affected75 at risk EG00110 events8 affected77 at risk EG00212 events10 affected152 at risk
Nausea	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG00016 events14 affected75 at risk EG0018 events8 affected77 at risk EG00224 events22 affected152 at risk
Oedema peripheral	General disorders	MedDRA 23	Systematic Assessment	EG0006 events4 affected75 at risk EG0015 events5 affected77 at risk EG00211 events9 affected152 at risk
Oral candidiasis	Infections and infestations	MedDRA 23	Systematic Assessment	EG0003 events2 affected75 at risk EG0016 events4 affected77 at risk EG0029 events6 affected152 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23	Systematic Assessment	EG0006 events5 affected75 at risk EG0014 events4 affected77 at risk EG00210 events9 affected152 at risk
Pneumonia	Infections and infestations	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0013 events3 affected77 at risk EG0027 events7 affected152 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG0012 events2 affected77 at risk EG0026 events6 affected152 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23	Systematic Assessment	EG00021 events16 affected75 at risk EG00122 events16 affected77 at risk EG00243 events32 affected152 at risk
Pyrexia	General disorders	MedDRA 23	Systematic Assessment	EG0008 events7 affected75 at risk EG0018 events8 affected77 at risk EG00216 events15 affected152 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 23	Systematic Assessment	EG00022 events15 affected75 at risk EG00116 events11 affected77 at risk EG00238 events26 affected152 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 23	Systematic Assessment	EG0005 events4 affected75 at risk EG0018 events7 affected77 at risk EG00213 events11 affected152 at risk
Respiratory tract infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0005 events5 affected75 at risk EG0012 events1 affected77 at risk EG0027 events6 affected152 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0006 events6 affected75 at risk EG0018 events8 affected77 at risk EG00214 events14 affected152 at risk
Urinary tract infection	Infections and infestations	MedDRA 23	Systematic Assessment	EG0004 events4 affected75 at risk EG00110 events6 affected77 at risk EG00214 events10 affected152 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23	Systematic Assessment	EG0008 events7 affected75 at risk EG0016 events6 affected77 at risk EG00214 events13 affected152 at risk
Weight decreased	Investigations	MedDRA 23	Systematic Assessment	EG0007 events7 affected75 at risk EG0018 events8 affected77 at risk EG00215 events15 affected152 at risk

ID	Term
D008175	Lung Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms