An Investigational Immuno-therapy Study Of Nivolumab In C... | NCT03377361

ID	Type	Description	Link
2017-001830-24	EudraCT Number

Name	Class
Novartis	INDUSTRY

Label	Type	Intervention Names
Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib	Experimental	Biological: Nivolumab Drug: Trametinib
Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib	Experimental	Biological: Nivolumab Drug: Trametinib Biological: Ipilimumab
Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib	Experimental	Biological: Nivolumab Drug: Trametinib Biological: Ipilimumab
Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib	Experimental	Biological: Nivolumab Drug: Trametinib Biological: Ipilimumab
Part 2 Cohort 5 (3L): Regorafenib	Experimental	Drug: Regorafenib
Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib	Experimental	Biological: Nivolumab Drug: Trametinib Biological: Ipilimumab

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Biological	Specified dose on specified days	Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib

Measure	Description	Time Frame
Dose Limiting Toxicities in Part 1 and Part 1A	Dose Limiting Toxicities are defined as adverse events have to be at least possibly related to study treatment, and not to disease progression, be clinically relevant and a clinically relevant shift from baseline.	4 weeks for Doublet Reginmen and 8 weeks for triplet Regimen
Safety Related Events in Part 1 and Part 1 A	Safety-related events in clinical trials include Adverse Events (AEs), Serious Adverse Events (SAEs), and deaths. An AE is any new or worsening medical issue in a participant receiving the study drug, regardless of its relation to the drug. This includes abnormal lab results, symptoms, or diseases. An SAE is a more severe AE that results in death, is life-threatening, requires or prolongs hospitalization, causes significant disability, involves a birth defect, or is deemed medically important-potentially jeopardizing the participant or requiring intervention, even if not immediately life-threatening. These definitions help ensure consistent reporting and evaluation of safety during clinical studies.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Thyroid Tests	Number of participants with clinical laboratory abnormalities in specific thyroid tests	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Liver Tests	Number of participants with clinical laboratory abnormalities in specific liver tests.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Overal Response Rate in Part 1B and Part 2

Measure	Description	Time Frame
Objective Response Rate in Part 1 and Part 1A	ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).	From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months)

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution - 0022		Birmingham	Alabama	35249	United States
Local Institution - 0027

Label	URL
BMS Clinical Trial Information	View source
BMS Clinical Trial Patient Recruiting	View source

ID	Title	Description
FG000	Part 1 Cohort 1	Trame 1.5mg Cont
FG001	Part 1 Cohort 1B	Trame 2 mg Int
FG002

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	May 3, 2023

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

Dose Limiting Toxicities in Part 1 and Part 1A

Dose Limiting Toxicities are defined as adverse events have to be at least possibly related to study treatment, and not to disease progression, be clinically relevant and a clinically relevant shift from baseline.

All treated participants in Part 1 and Part 1A

Posted

Number

Participants

4 weeks for Doublet Reginmen and 8 weeks for triplet Regimen

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont
OG005	Part 1A Cohort 3	Trame 1.5mg Int
OG006	Part 1A Cohort 3B	Trame 2mg Int

Units	Counts
Participants	OG0003 OG0013 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Primary

Safety Related Events in Part 1 and Part 1 A

Safety-related events in clinical trials include Adverse Events (AEs), Serious Adverse Events (SAEs), and deaths. An AE is any new or worsening medical issue in a participant receiving the study drug, regardless of its relation to the drug. This includes abnormal lab results, symptoms, or diseases. An SAE is a more severe AE that results in death, is life-threatening, requires or prolongs hospitalization, causes significant disability, involves a birth defect, or is deemed medically important-potentially jeopardizing the participant or requiring intervention, even if not immediately life-threatening. These definitions help ensure consistent reporting and evaluation of safety during clinical studies.

All treated participants in Part 1 and Part 1A

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont

Primary

Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Thyroid Tests

Number of participants with clinical laboratory abnormalities in specific thyroid tests

All treated participants in Part 1 and Part 1A

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont

Primary

Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Liver Tests

Number of participants with clinical laboratory abnormalities in specific liver tests.

All treated participants in Part 1 and Part 1A with atleast 1 On-Treatment Liver Test Measurement

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont

Primary

Overal Response Rate in Part 1B and Part 2

ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).

All Randomized Participants in Part 1B and Part 2

Posted

Number

95% Confidence Interval

Percentage of Participants

Approximately up to 30 Months

ID	Title	Description
OG000	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5
OG001	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5
OG002	Part 2 Treatment 2	Regorafenib 80/160

Units	Counts
Participants	OG000

Secondary

Objective Response Rate in Part 1 and Part 1A

ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).

All treated participants in Part 1 and Part 1A

Posted

Number

95% Confidence Interval

Percentage of Participants

From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A

Secondary

Disease Control Rate in Part 1 and Part 1A

The disease control rate (DCR) is defined as the percentage of participants whose BOR is either confirmed CR or confirmed PR or stable disease (SD)

All treated participants in Part 1 and Part 1A

Posted

Number

95% Confidence Interval

Percentage of Participants

From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont

Secondary

Duration of Response in Part 1 and Part 1A

DOR for a participant with a BOR of confirmed CR or PR, is defined as the time between the date of first confirmed response and the date of the first objectively documented tumor progression per RECIST 1.1 or death, whichever occurs first.

All treated participants in Part 1 and Part 1A who had a response

Posted

Median

95% Confidence Interval

Months

Approximately up to 20 Months

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont

Secondary

Time to Response in Part 1 and Part 1A

Time to response (TTR) is defined for participants who had a confirmed CR or PR as the time from the first dosing date to the date of first documented CR or PR per RECIST 1.1.

All treated participants in Part 1 and Part 1A who had a response

Posted

Median

Full Range

Months

From the first dosing date to the date of first documented CR or PR per RECIST 1.1. (Approximately on average 10 months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont

Secondary

Progression Free Survival in Part 1 and Part 1A

PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression per RECIST 1.1 (ie, radiologic) or death due to any cause, whichever occurs first.

All treated participants in Part 1 and Part 1A

Posted

Median

95% Confidence Interval

Months

from the first dosing date to the date of first objectively documented disease progression or death, whichever occurs first (Approximately up to 21 months)

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A

Secondary

Overall Survival in Part 1 and Part 1A

OS for a participant is defined as the time from the first dosing date to the date of death due to any cause. A participant who has not died will be censored at last known date alive.

All treated participants in Part 1 and Part 1A

Posted

Median

95% Confidence Interval

Months

Approximately up to 69 Months

ID	Title	Description
OG000	Part 1 Cohort 1	Trame 1.5mg Cont
OG001	Part 1 Cohort 1B	Trame 2 mg Int
OG002	Part 1 Cohort 1D	Trame 2mg Cont
OG003	Part 1A Cohort 2	Trame 1.5mg Cont
OG004	Part 1A Cohort 2A	Trame 1mg Cont
OG005

Secondary

Safety Related Events in Part 1B and Part 2

All Treated Participants in Part 1B and Part 2

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)

ID	Title	Description
OG000	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5
OG001	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5
OG002	Part 2 Treatment 2	Regorafenib 80/160

Secondary

Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Thyroid Tests

Number of participants with clinical laboratory abnormalities in specific thyroid tests

All Treated Participants in Part 1B and Part 2 with atleast 1 On-Treatment TSH Measurement

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)

ID	Title	Description
OG000	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5
OG001	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5
OG002	Part 2 Treatment 2	Regorafenib 80/160

Units	Counts
Participants	OG000

Secondary

Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Liver Tests

Number of participants with clinical laboratory abnormalities in specific liver tests.

All Treated Participants in Part 1B and Part 2 with atleast 1 On-Treatment Liver test Measurement

Posted

Count of Participants

Participants

Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)

ID	Title	Description
OG000	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5
OG001	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5
OG002	Part 2 Treatment 2	Regorafenib 80/160

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG0030 affected7 at risk EG0040 affected3 at risk EG0050 affected3 at risk EG0061 affected7 at risk EG0071 affected82 at risk EG0082 affected121 at risk EG0091 affected57 at risk
Atrial fibrillation	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Cardiac arrest	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cardiac failure	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cardiac failure congestive	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Adrenal insufficiency	Endocrine disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypothyroidism	Endocrine disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Detachment of retinal pigment epithelium	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Eyelid ptosis	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Anal fistula	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ascites	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Colitis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Enteritis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gastrooesophageal haemorrhage	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Haematochezia	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ileus	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Immune-mediated enterocolitis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intestinal ischaemia	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intestinal perforation	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intestinal pseudo-obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Nausea	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pancreatitis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rectal perforation	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Asthenia	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cardiac death	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Disease progression	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Influenza like illness	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Localised oedema	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Non-cardiac chest pain	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Oedema peripheral	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pyrexia	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Acute cholecystitis necrotic	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Acute hepatic failure	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Biliary cast syndrome	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Biliary obstruction	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Cholangitis	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hepatic failure	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hepatitis	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Immune-mediated hepatitis	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Jaundice	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Liver disorder	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Malignant biliary obstruction	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Bacteraemia	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
COVID-19	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cellulitis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Clostridium difficile colitis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Enterocolitis infectious	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Listeriosis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonia	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonia pneumococcal	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Proteus infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sepsis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Septic shock	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Soft tissue infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Stoma site abscess	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Stoma site infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Streptococcal infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urinary tract infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urosepsis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vascular device infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Limb injury	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Overdose	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Amylase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood bilirubin increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood creatinine increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood lactic acid increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ejection fraction decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gamma-glutamyltransferase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lipase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Type 1 diabetes mellitus	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Brain neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Metastases to eye	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cerebrovascular accident	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hepatic encephalopathy	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyponatraemic encephalopathy	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Seizure	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Spinal cord compression	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Syncope	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Transient ischaemic attack	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Confusional state	Psychiatric disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Delirium	Psychiatric disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Mental status changes	Psychiatric disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Acute kidney injury	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hydronephrosis	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Intermenstrual bleeding	Reproductive system and breast disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pelvic pain	Reproductive system and breast disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Erythrodermic psoriasis	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Deep vein thrombosis	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Embolism	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Extrinsic iliac vein compression	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertension	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0023 affected6 at risk EG0034 affected7 at risk EG0041 affected3 at risk EG0052 affected3 at risk EG0064 affected7 at risk EG00718 affected82 at risk EG00836 affected121 at risk EG00912 affected57 at risk
Increased tendency to bruise	Blood and lymphatic system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cardiac disorder	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Palpitations	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sinus bradycardia	Cardiac disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Tachycardia	Cardiac disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vertigo	Ear and labyrinth disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperthyroidism	Endocrine disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hypothyroidism	Endocrine disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Diplopia	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Dry eye	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Iridocyclitis	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ocular hyperaemia	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Retinopathy	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Subretinal fluid	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Swelling of eyelid	Eye disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Uveitis	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vision blurred	Eye disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Visual impairment	Eye disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ascites	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Constipation	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0023 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	27.1	Systematic Assessment	EG0003 affected3 at risk EG0012 affected3 at risk EG0024 affected6 at risk EG003
Diarrhoea haemorrhagic	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dry mouth	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Flatulence	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Gingival bleeding	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Haematochezia	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Nausea	Gastrointestinal disorders	27.1	Systematic Assessment	EG0003 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Proctalgia	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Asthenia	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Chills	General disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Early satiety	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	27.1	Systematic Assessment	EG0003 affected3 at risk EG0011 affected3 at risk EG0024 affected6 at risk EG003
Gait disturbance	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Influenza like illness	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Malaise	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Mucosal inflammation	General disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Oedema peripheral	General disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0011 affected3 at risk EG0023 affected6 at risk EG003
Pain	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Pyrexia	General disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Thirst	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Xerosis	General disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
COVID-19	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Candida infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cellulitis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gingivitis	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Mucosal infection	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Paronychia	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pneumonia	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Rash pustular	Infections and infestations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urinary tract infection	Infections and infestations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Burns first degree	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Blood albumin decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood alkaline phosphatase increased	Investigations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Blood bilirubin increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood calcium decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood creatinine increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood lactate dehydrogenase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood magnesium decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood phosphorus decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood potassium decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood sodium decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ejection fraction decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lipase increased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Lymphocyte count decreased	Investigations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Platelet count decreased	Investigations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Weight decreased	Investigations	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
White blood cell count decreased	Investigations	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0024 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0023 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Coccydynia	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cerebral ischaemia	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Disturbance in attention	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dizziness	Nervous system disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Dysgeusia	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyskinesia	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Headache	Nervous system disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Hypoaesthesia	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Presyncope	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Taste disorder	Nervous system disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Anxiety	Psychiatric disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Confusional state	Psychiatric disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Insomnia	Psychiatric disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dysuria	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Haematuria	Renal and urinary disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hydronephrosis	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Proteinuria	Renal and urinary disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pelvic pain	Reproductive system and breast disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blister	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0002 affected3 at risk EG0013 affected3 at risk EG0025 affected6 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pruritus allergic	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Skin fissures	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Flushing	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hot flush	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertension	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk EG0022 affected6 at risk EG003
Hypotension	Vascular disorders	27.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vena cava thrombosis	Vascular disorders	27.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Part 1 Cohort 1	Trame 1.5mg Cont
BG001	Part 1 Cohort 1B	Trame 2 mg Int
BG002	Part 1 Cohort 1D	Trame 2mg Cont
BG003	Part 1A Cohort 2	Trame 1.5mg Cont
BG004	Part 1A Cohort 2A	Trame 1mg Cont
BG005	Part 1A Cohort 3	Trame 1.5mg Int
BG006	Part 1A Cohort 3B	Trame 2mg Int
BG007	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5
BG008	Part 2 Treatment 2	Regorafenib 80/160
BG009	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5
BG010	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1 Cohort 1	Trame 1.5 mg Cont	2	3	2	3	3	3
EG001	Part 1 Cohort 1B	Trame 2 mg Int	2	3	0	3	3	3
EG002	Part 1 Cohort 1D	Trame 2 mg Cont	6	6	5	6	6	6
EG003	Part 1A Cohort 2	Trame 1.5 mg Cont	3	7	3	7	7	7
EG004	Part 1A Cohort 2A	Trame 1 mg Cont	2	3	0	3	3	3
EG005	Part 1A Cohort 3	Trame 1.5 mg Int	3	3	2	3	3	3
EG006	Part 1A Cohort 3B	Trame 2 mg Int	5	7	3	7	7	7
EG007	Part 1B	Nivo 6 + Ipi 1 + Trame 1.5	49	82	42	82	82	82
EG008	Part 2 Treatment 1	Nivo 6 + Ipi 1 + Trame 1.5	108	124	79	121	121	121
EG009	Part 2 Treatment 2	Regorafenib 80/160	55	61	33	57	55	57

ID	Term
D000077594	Nivolumab
C560077	trametinib
D000074324	Ipilimumab
C559147	regorafenib