Study of Pembrolizumab (MK-3475) vs. Best Supportive Care... | NCT02702401

ID	Type	Description
163456	Registry Identifier	JAPIC-CTI
MK-3475-240	Other Identifier	Merck
KEYNOTE-240	Other Identifier	Merck
2015-004567-36	EudraCT Number

Label	Type	Description	Intervention Names
Pembrolizumab+Best Supportive Care	Experimental	Participants receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).	Biological: Pembrolizumab Other: Best Supportive Care
Placebo+Best Supportive Care	Placebo Comparator	Participants receive a placebo IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.	Drug: Placebo Other: Best Supportive Care

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	IV infusion	Pembrolizumab+Best Supportive Care

Measure	Description	Time Frame
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for PFS was performed for the first pembrolizumab course at protocol specified cut off of 26-Mar-2018.	Through database cutoff date of 26-Mar-2018 (Up to approximately 21 months)
Overall Survival (OS)	OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for OS was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.	Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

Measure	Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The ORR was analyzed using the Miettinen & Nurminen method. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented. Final analyses for ORR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a HCC diagnosis confirmed by radiology, histology or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach.
Has a Child-Pugh Class A liver score within 7 days of first dose of study drug.
Has a predicted life expectancy >3 months.
Has at least one measurable lesion based on RECIST 1.1 as confirmed by the blinded central imaging vendor.
Has a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 7 days of first dose of study drug.
Has documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib.
Participants with chronic infection by Hepatitis C Virus (HCV) who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, participants with successful HCV treatment are allowed as long as there are ≥4 weeks between achieving sustained viral response (SVR12) and start of study drug.
Has controlled Hepatitis B Virus (HBV) infection.
Is willing to use an adequate method of contraception for the course of the study through at least 120 days or longer based on local regulation after the last dose of study drug (male and female participants of childbearing potential).
Demonstrates adequate organ function.

Exclusion Criteria:

Is currently participating, or has participated in a study of an investigational agent and received study drug, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of study drug. Participants must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events (AEs) due to any prior therapy.
Has received sorafenib within 14 days of first dose of study drug.
Has had esophageal or gastric variceal bleeding within the last 6 months.
Has clinically apparent ascites on physical examination. Note: ascites detectable on imaging studies only ARE allowed.
Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
Has had a solid organ or hematologic transplant.
Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib, prior to the start of study drug.
Has a known severe hypersensitivity (≥Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug.
Has had major surgery to liver or other site within 4 weeks prior to the first dose of study drug.
Has had minor surgery (i.e., simple excision, tooth extraction) ≤7 days prior to the first dose of study drug (Cycle 1, Day 1).
Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to starting study drug.
Has a diagnosed additional malignancy within 3 years prior to first dose of study drug with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers.
Has known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has a history of non-infectious pneumonitis that required steroids or current pneumonitis.
Has an active infection requiring systemic therapy.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the first dose of study drug through 120 days or longer based on local regulation after the last dose of study drug.
Has received prior immunotherapy including anti-programmed cell death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in Merck pembrolizumab (MK-3475) studies.
Has a known history of human immunodeficiency virus (HIV).
Has dual active HBV infection and HCV infection at study entry.
Has received a live vaccine within 30 days of planned start of study drug (Cycle 1, Day 1).

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
31790344	Result	Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.
41453647

Label	URL
Merck Oncology Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS best supportive care (BSC). Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 3, 2021

ID	Title	Description
BG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS best supportive care (BSC). Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
BG001	Placebo + Best Supportive Care	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000278 BG001135 BG002413

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

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for PFS was performed for the first pembrolizumab course at protocol specified cut off of 26-Mar-2018.

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through database cutoff date of 26-Mar-2018 (Up to approximately 21 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001	Placebo + Best Supportive Care	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.

Units	Counts
Participants	OG000278 OG001135

Title

Denominators

Categories

Title	Measurements
	OG0003.0(2.8 to 4.1) OG0012.8(2.5 to 4.1)

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		Log Rank	One-sided p-value stratified by geographic region, macrovascular invasion and alfa-fetoprotein level.	0.0186		Hazard Ratio (HR)	0.775			2-Sided	95	0.609	0.987			Cox regression model with Efron's method (treatment as covariate) stratified by geographic region, macrovascular invasion and alfa-fetoprotein level		Superiority

Primary

Overall Survival (OS)

OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for OS was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001	Placebo + Best Supportive Care	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.

Secondary

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The ORR was analyzed using the Miettinen & Nurminen method. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented. Final analyses for ORR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001	Placebo + Best Supportive Care

Secondary

Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DCR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions), Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), or Stable Disease (SD) per RECIST 1.1 after ≥6 weeks as assessed by Blinded Independent Central Review (BICR). The DCR was analyzed using the Miettinen & Nurminen method. The percentage of participants who experienced a CR, PR, or SD is presented. Final analyses for DCR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001	Placebo + Best Supportive Care

Secondary

Time to Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. If there was no documented disease progression, TTP was censored at last tumor assessment date. The TTP was analyzed using the product-limit (Kaplan-Meier) method for censored data. TTP per RECIST 1.1 is presented for all participants. Final analyses for TTP was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001	Placebo + Best Supportive Care

Secondary

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DOR was determined in participants who demonstrated a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. The DOR was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for DOR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included all randomized participants who demonstrated at least a partial response. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

From time of first documented evidence of CR or PR through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).

Secondary

Number of Participants Who Experienced At Least One Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. Final analyses for AE was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included participants who received ≥1 dose of study treatment. Participants were grouped by actual treatment received.

Posted

Count of Participants

Participants

Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
OG001

Secondary

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. Final analyses for AE was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.

The analysis population included participants who received ≥1 dose of study treatment. Participants were grouped by actual treatment received.

Posted

Count of Participants

Participants

From Day 1 through end of treatment (Up to approximately 24 months)

ID	Title	Description
OG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0016 events5 affected134 at risk EG0020 events0 affected7 at risk
Immune thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0012 events2 affected134 at risk EG0020 events0 affected7 at risk
Cardiac arrest	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Myocardial infarction	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pericardial effusion	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hypophysitis	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hypothyroidism	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Blindness unilateral	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Macular hole	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Retinal detachment	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Retinal vein occlusion	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Ascites	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00014 events13 affected279 at risk EG0015 events5 affected134 at risk EG0020 events0 affected7 at risk
Colitis	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Diverticular fistula	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Gastritis	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Gastroduodenal ulcer	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Intra-abdominal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0004 events3 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Varices oesophageal	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Chest pain	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Death	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
General physical health deterioration	General disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Influenza like illness	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Mucosal inflammation	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hepatic cyst	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0012 events2 affected134 at risk EG0020 events0 affected7 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Jaundice	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Contrast media allergy	Immune system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Bronchitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Cellulitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Gastroenteritis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hepatitis B	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Hepatitis C	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Influenza	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Liver abscess	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Mycobacterial infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Peritonitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Peritonitis bacterial	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Pleural infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pneumonia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0006 events6 affected279 at risk EG0013 events3 affected134 at risk EG0020 events0 affected7 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Pneumonia mycoplasmal	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Thrombophlebitis septic	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Vascular procedure complication	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0007 events7 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0009 events9 affected279 at risk EG0014 events4 affected134 at risk EG0020 events0 affected7 at risk
Blood bilirubin increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0008 events8 affected279 at risk EG0013 events2 affected134 at risk EG0020 events0 affected7 at risk
Blood creatinine increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0021 events1 affected7 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Polymyalgia rheumatica	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Insulinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Oral neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Tumour rupture	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Cerebral infarction	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Seizure	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Syncope	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Mental status changes	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Renal failure	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Lichenoid keratosis	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk
Aortic stenosis	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0011 events1 affected134 at risk EG0020 events0 affected7 at risk
Hypotension	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0020 events0 affected7 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG00029 events27 affected279 at risk EG00118 events11 affected134 at risk EG0020 events0 affected7 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0011 events1 affected134 at risk EG0021 events1 affected7 at risk
Hypothyroidism	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG00014 events13 affected279 at risk EG0017 events7 affected134 at risk EG0020 events0 affected7 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00051 events39 affected279 at risk EG0019 events9 affected134 at risk EG0020 events0 affected7 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00027 events25 affected279 at risk EG00114 events10 affected134 at risk EG0020 events0 affected7 at risk
Ascites	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00015 events15 affected279 at risk EG0018 events8 affected134 at risk EG0020 events0 affected7 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00033 events28 affected279 at risk EG00116 events15 affected134 at risk EG0020 events0 affected7 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00074 events49 affected279 at risk EG00124 events20 affected134 at risk EG0020 events0 affected7 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0006 events5 affected279 at risk EG0012 events2 affected134 at risk EG0021 events1 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00041 events33 affected279 at risk EG00121 events20 affected134 at risk EG0020 events0 affected7 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Toothache	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0004 events3 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00041 events26 affected279 at risk EG0019 events5 affected134 at risk EG0020 events0 affected7 at risk
Asthenia	General disorders	MedDRA 24.0	Systematic Assessment	EG00035 events26 affected279 at risk EG00117 events15 affected134 at risk EG0020 events0 affected7 at risk
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG00060 events51 affected279 at risk EG00132 events31 affected134 at risk EG0022 events2 affected7 at risk
Oedema peripheral	General disorders	MedDRA 24.0	Systematic Assessment	EG00039 events32 affected279 at risk EG00120 events17 affected134 at risk EG0021 events1 affected7 at risk
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG00027 events25 affected279 at risk EG00122 events15 affected134 at risk EG0020 events0 affected7 at risk
Herpes zoster	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00049 events45 affected279 at risk EG00112 events12 affected134 at risk EG0020 events0 affected7 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00058 events55 affected279 at risk EG00121 events18 affected134 at risk EG0020 events0 affected7 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00020 events20 affected279 at risk EG0019 events9 affected134 at risk EG0020 events0 affected7 at risk
Blood bilirubin increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00059 events46 affected279 at risk EG00118 events16 affected134 at risk EG0020 events0 affected7 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00019 events18 affected279 at risk EG0017 events7 affected134 at risk EG0020 events0 affected7 at risk
Platelet count decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG00016 events13 affected279 at risk EG0012 events2 affected134 at risk EG0021 events1 affected7 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG00051 events47 affected279 at risk EG00123 events21 affected134 at risk EG0020 events0 affected7 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG00021 events12 affected279 at risk EG0017 events7 affected134 at risk EG0020 events0 affected7 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG00025 events21 affected279 at risk EG0017 events7 affected134 at risk EG0020 events0 affected7 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG00037 events33 affected279 at risk EG00119 events17 affected134 at risk EG0020 events0 affected7 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG00031 events29 affected279 at risk EG00114 events13 affected134 at risk EG0020 events0 affected7 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0008 events5 affected279 at risk EG0013 events3 affected134 at risk EG0021 events1 affected7 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0004 events4 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG00023 events20 affected279 at risk EG0017 events5 affected134 at risk EG0020 events0 affected7 at risk
Insomnia	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG00012 events12 affected279 at risk EG00110 events8 affected134 at risk EG0020 events0 affected7 at risk
Sleep disorder	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Dysuria	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0011 events1 affected134 at risk EG0021 events1 affected7 at risk
Penile erythema	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected279 at risk EG0010 events0 affected134 at risk EG0021 events1 affected7 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG00032 events24 affected279 at risk EG00127 events24 affected134 at risk EG0021 events1 affected7 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG00019 events19 affected279 at risk EG00116 events14 affected134 at risk EG0020 events0 affected7 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected279 at risk EG0012 events1 affected134 at risk EG0021 events1 affected7 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected279 at risk EG0013 events3 affected134 at risk EG0021 events1 affected7 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG00066 events53 affected279 at risk EG00118 events17 affected134 at risk EG0020 events0 affected7 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG00042 events35 affected279 at risk EG0018 events7 affected134 at risk EG0020 events0 affected7 at risk
Hypertension	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG00010 events10 affected279 at risk EG00114 events8 affected134 at risk EG0020 events0 affected7 at risk

ID	Term
D006528	Carcinoma, Hepatocellular
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + Best Supportive Care	Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).	246	279	106	279	240	279
EG001	Placebo + Best Supportive Care	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.	124	134	37	134	109	134
EG002	Pembrolizumab Second Course	Participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 17 cycles (up to ~1 year).	3	7	3	7	7	7