An Investigational Immuno-therapy Study to Evaluate Safet... | NCT02320058

Label	Type	Description	Intervention Names
Nivolumab and Ipilimumab	Experimental	Induction Phase: Nivolumab + Ipilimumab infusion intravenously Maintenance Phase: Nivolumab infusion intravenously	Drug: Ipilimumab Drug: Nivolumab

Name	Type	Description	Arm Group Labels	Other Names
Ipilimumab	Drug		Nivolumab and Ipilimumab	Yervoy
Nivolumab

Measure	Description	Time Frame
Intracranial Clinical Benefit Rate (CBR)	Intracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of >6 months, as determined by modified RECIST 1.1 criteria for index intracranial lesions based on investigator review.	Up to 66 months

Measure	Description	Time Frame
Intracranial Objective Response Rate (ORR)	Investigator-Assessed Intracranial Objective Response Rate (ORR) per modified RECIST 1.1 criteria is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.	Up to 66 months

Eligibility Module

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

1. Target Population

Histologically confirmed malignant melanoma with measurable metastases in the brain. Both asymptomatic and symptomatic patients.
Cohort A (asymptomatic patients): At least 1 measurable brain metastasis ≥ 0.5 cm in and ≤ 3 cm in longest diameter that has not been previously irradiated. No clinical requirement for local intervention (surgery, radiosurgery, corticosteroid therapy) or other systemic therapy

Cohort B (symptomatic patients): Subjects with neurologic signs and symptoms related to metastatic brain lesions are eligibile. Subjects must have at least 1 measurable brain metastasis ≥ 0.5 cm in and ≤ 3 cm in longest diameter that has not been previously irradiated. No immediate requirement (within 3 weeks prior to first treatment) for local intervention (surgery, radiosurgery, corticosteroid therapy). Steroid use is permitted as defined in the protocol.
Prior stereotactic radiotherapy (SRT) and prior excision of up to 3 melanoma brain metastases is permitted if there has been complete recovery, with no neurologic sequelae, and measurable lesions remain. Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable. lesions or prior excision must have occurred ≥ 3 weeks before the start of dosing for this study
Must have tumor tissue available for biomarker analysis. Biopsy should be excisional, incisional, punch, or core needle
Cohort A (asymptomatic): Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy within 10 days prior to first treatment.

Cohort B (symptomatic): Subjects with neurologic signs and symptoms related to metastatic brain lesions are eligible per Amendment 02. Subjects with neurologic signs and symptoms may be treated with a total daily dose of no more than 4 mg of dexamethasone that is stable or tapering for 10 days prior to first treatment. Subjects with neurologic signs and symptoms who are not being treated with steroids are eligible for Cohort B and should have no experience of seizure within 10 days prior to first treatment.
Allowable prior therapy:
1. Approved adjuvant therapies, which may include molecularly-targeted agents, IFN α, and ipilimumab. Patients who received ipilimumab as adjuvant therapy must have a 6 month washout before receiving any dosing on this study
2. For advanced disease, interleukin-2 at any dose and/or IFN-α (any formulation, no washout required); MEK and BRAF inhibitors: washout for at least 4 weeks prior to the start of dosing in this study
3. Steroids for physiological replacement are allowed.
Cohort A (asymptomatic): ECOG performance status ≤1 Cohort B (symptomatic): ECOG performance status ≤2

Exclusion Criteria:

2. Target Disease Exceptions

History of known leptomeningeal involvement (lumbar puncture not required)
Previous stereotactic or highly conformal radiotherapy within 3 weeks before the start of dosing for this study. Note the stereotactic radiotherapy field must not have included the brain index lesion(s)
Brain lesions >3 lesions which were previously treated with SRT
Brain lesion size > 3cm 3. Medical History and Concurrent Diseases

a) History of whole brain irradiation b) Subjects with an active, known or suspected autoimmune disease c) Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled d) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. For any prior invasive malignancy, at least 5 years must have elapsed since curative therapy and patients must have no residual sequelae of prior therapy e) Cohort A (asymptomatic): The use of corticosteroids is not allowed within 10 days prior to first treatment (based upon 5 times the expected half life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the sponsor Medical Monitor is required to determine the washout period prior to initiating study treatment Cohort B (symptomatic): Subjects with neurologic sign and symptoms related to brain metastases who are being treated with a total daily dose of higher than 4 mg dexamethasone or equivalent within 10 prior to the start of treatment with study drug are excluded.

4. Physical and Laboratory Test Findings

Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on ART-due to the unknown effects of HIV on the immune response to combined nivolumab plus ipilimumab or the unique toxicity spectrum of these drugs in patients with HIV

5. Allergies and Adverse Drug Reaction

a) History of allergy to study drug components b) History of severe hypersensitivity reaction to any monoclonal antibody

6. Other Exclusion Criteria

Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria

Other protocol defined inclusion/exclusion criteria could apply

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

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope		Duarte	California	91010	United States
Angeles Clinic and Research Institute

PubMed Identifier	Type	Citation	Retractions
39752606	Derived	Huang RY, Youssef G, Nelson T, Wen PY, Forsyth P, Hodi FS, Margolin K, Algazi AP, Hamid O, Lao CD, Ernstoff MS, Moschos SJ, Atkins MB, Postow MA, Reardon DA, Grootendorst DJ, Leung D, Askelson M, Ritchings C, Tawbi HA. Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204. J Clin Oncol. 2025 Apr;43(10):1210-1218. doi: 10.1200/JCO.24.00953. Epub 2025 Jan 3.
36006879

Label	URL
BMS Clinical Trial Information	View source

ID	Title	Description
FG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
FG001	Cohort B

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 13, 2017	Sep 8, 2021

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

Intracranial Clinical Benefit Rate (CBR)

Intracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of >6 months, as determined by modified RECIST 1.1 criteria for index intracranial lesions based on investigator review.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants	OG000101 OG00118

Title

Denominators

Categories

Title	Measurements
	OG00057.4(47.2 to 67.2) OG00116.7(3.6 to 41.4)

Secondary

Intracranial Objective Response Rate (ORR)

Investigator-Assessed Intracranial Objective Response Rate (ORR) per modified RECIST 1.1 criteria is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Intracranial Progression Free Survival (PFS)

Intracranial progression-free survival (PFS) per modified RECIST 1.1 criteria is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.

All treated participants

Posted

Median

95% Confidence Interval

Months

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Secondary

Extracranial Clinical Benefit Rate (CBR)

Extracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of >6 months, as determined by RECIST 1.1 criteria for index extracranial lesions based on investigator review.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Extracranial Objective Response Rate (ORR)

Extracranial Objective Response Rate (ORR) per RECIST 1.1 criteria is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Extracranial Progression Free Survival (PFS)

Extracranial progression-free survival (PFS) per RECIST 1.1 criteria is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.

All treated participants

Posted

Median

95% Confidence Interval

Months

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Secondary

Global Clinical Benefit Rate (CBR)

Investigator-assessed global (intracranial + extracranial) clinical benefit rate (CBR) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of >6 months

All treated participants

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts

Secondary

Global Objective Response Rate (ORR)

Investigator-assessed global objective response rate (ORR) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Global Progression Free Survival (PFS)

Investigator-assessed global progression free survival (PFS) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.

All treated participants

Posted

Median

95% Confidence Interval

Months

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Secondary

Overall Survival (OS)

Overall Survival (OS) is defined as the time from the date of the start of treatment until the date of death. For participants who have not died, OS will be censored at the recorded last date of participant contact, and participants with a missing recorded last date of contact will be censored at the last date the participant was known to be alive.

All treated participants

Posted

Median

95% Confidence Interval

Months

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs)

Number of participants with any grade of adverse events (AEs) and any grade of serious adverse events (SAEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.0)

All treated participants

Posted

Count of Participants

Participants

From first dose to 30 days post last dose (Up to 66 months)

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants

Secondary

Number of Participants Deaths

Number of participants who died due to any cause.

All treated participants

Posted

Count of Participants

Participants

Up to 66 months

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Laboratory Abnormalities in Specific Liver Tests

Number of participants with laboratory abnormalities in specific liver tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized:

ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN
Total bilirubin > 2 x ULN
Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN
Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter

Posted

Count of Participants

Participants

From first dose to 30 days post last dose (Up to 66 months)

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.

Secondary

Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests

Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of subjects with the following laboratory abnormalities from on-treatment evaluations will be summarized:

TSH value > ULN and
with baseline TSH value <= ULN
with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test
with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test
with FT3/FT4 missing within 2-week window after the abnormal TSH test.
TSH < LLN and
with baseline TSH value >= LLN
with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test
with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test
with FT3/FT4 missing within 2-week window after the abnormal TSH test

All treated participants with at least one on-treatment TSH measurement

Posted

Count of Participants

Participants

From first dose to 30 days post last dose (Up to 66 months)

ID	Title	Description
OG000	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
OG001	Cohort B

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
WARM TYPE HAEMOLYTIC ANAEMIA	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ACUTE CORONARY SYNDROME	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
ANGINA PECTORIS	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk
MYOCARDITIS	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ADRENAL INSUFFICIENCY	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0010 affected18 at risk
HYPERTHYROIDISM	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk
HYPOPHYSITIS	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0010 affected18 at risk
VISION BLURRED	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
COLITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0011 affected18 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0011 affected18 at risk
DUODENITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
IMMUNE-MEDIATED PANCREATITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
PANCREATITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
SMALL INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
VOMITING	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
DEATH	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
FATIGUE	General disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
INFLUENZA LIKE ILLNESS	General disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
MUCOSAL INFLAMMATION	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
PYREXIA	General disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
CHOLELITHIASIS	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
HEPATITIS ACUTE	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
CYTOKINE RELEASE SYNDROME	Immune system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
BACILLUS INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
CELLULITIS ORBITAL	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
CLOSTRIDIUM DIFFICILE INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
MENINGITIS BACTERIAL	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
ORBITAL INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PNEUMONIA	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
RASH PUSTULAR	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
SEPSIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
SKIN INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
SOFT TISSUE INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
STAPHYLOCOCCAL SEPSIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
HIP FRACTURE	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
SYNOVIAL RUPTURE	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0010 affected18 at risk
AMYLASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0010 affected18 at risk
LIPASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
TYPE 1 DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
MYOSITIS	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
INTRACRANIAL TUMOUR HAEMORRHAGE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
MALIGNANT NEOPLASM PROGRESSION	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0019 affected18 at risk
TUMOUR PSEUDOPROGRESSION	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
BRAIN OEDEMA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk
CEREBRAL HAEMORRHAGE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
DYSAESTHESIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
HAEMORRHAGE INTRACRANIAL	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk
HEADACHE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
HEMIPARESIS	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ISCHAEMIC STROKE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
LACUNAR INFARCTION	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
METABOLIC ENCEPHALOPATHY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
PARAESTHESIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
PARTIAL SEIZURES	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PERIPHERAL MOTOR NEUROPATHY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
PRESYNCOPE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
SEIZURE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
SYNCOPE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk
IMMUNE-MEDIATED NEPHRITIS	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
NEPHRITIS	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0010 affected18 at risk
GRANULOMATOUS PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
LUNG DISORDER	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
EMBOLISM	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0010 affected18 at risk
HYPOTENSION	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0010 affected18 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG00016 affected101 at risk EG0011 affected18 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
SINUS TACHYCARDIA	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0011 affected18 at risk
TACHYCARDIA	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
EAR PAIN	Ear and labyrinth disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0012 affected18 at risk
TINNITUS	Ear and labyrinth disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
ADRENAL INSUFFICIENCY	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG00010 affected101 at risk EG0010 affected18 at risk
HYPERTHYROIDISM	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG00014 affected101 at risk EG0010 affected18 at risk
HYPOGONADISM	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
HYPOPHYSITIS	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0012 affected18 at risk
HYPOTHYROIDISM	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG00026 affected101 at risk EG0011 affected18 at risk
THYROIDITIS	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
IRITIS	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0012 affected18 at risk
OCULAR HYPERAEMIA	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
PHOTOPHOBIA	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
PHOTOPSIA	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0012 affected18 at risk
VISION BLURRED	Eye disorders	MedDRA 23.1	Systematic Assessment	EG00014 affected101 at risk EG0015 affected18 at risk
VISUAL ACUITY REDUCED	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
VISUAL IMPAIRMENT	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0012 affected18 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00019 affected101 at risk EG0013 affected18 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0008 affected101 at risk EG0010 affected18 at risk
ABDOMINAL TENDERNESS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
APHTHOUS ULCER	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
ASCITES	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00014 affected101 at risk EG0013 affected18 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00051 affected101 at risk EG0018 affected18 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0011 affected18 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0008 affected101 at risk EG0010 affected18 at risk
FLATULENCE	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0012 affected18 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00053 affected101 at risk EG00110 affected18 at risk
ORAL DISORDER	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0012 affected18 at risk
VOMITING	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00028 affected101 at risk EG0016 affected18 at risk
ASTHENIA	General disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
CHILLS	General disorders	MedDRA 23.1	Systematic Assessment	EG00015 affected101 at risk EG0013 affected18 at risk
DISEASE PROGRESSION	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
FATIGUE	General disorders	MedDRA 23.1	Systematic Assessment	EG00069 affected101 at risk EG0018 affected18 at risk
GAIT DISTURBANCE	General disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0012 affected18 at risk
INFLUENZA LIKE ILLNESS	General disorders	MedDRA 23.1	Systematic Assessment	EG00013 affected101 at risk EG0011 affected18 at risk
LOCALISED OEDEMA	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
MALAISE	General disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
OEDEMA	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA 23.1	Systematic Assessment	EG00018 affected101 at risk EG0013 affected18 at risk
PAIN	General disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0011 affected18 at risk
PYREXIA	General disorders	MedDRA 23.1	Systematic Assessment	EG00028 affected101 at risk EG0014 affected18 at risk
CYTOKINE RELEASE SYNDROME	Immune system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
HYPERSENSITIVITY	Immune system disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
CRYPTOCOCCAL FUNGAEMIA	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
IMPETIGO	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
ORAL CANDIDIASIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0011 affected18 at risk
SINUSITIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0008 affected101 at risk EG0011 affected18 at risk
TINEA CRURIS	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0011 affected18 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0008 affected101 at risk EG0011 affected18 at risk
ESCHAR	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
FALL	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
PROCEDURAL PAIN	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00041 affected101 at risk EG0016 affected18 at risk
AMYLASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00017 affected101 at risk EG0011 affected18 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00039 affected101 at risk EG0013 affected18 at risk
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00012 affected101 at risk EG0012 affected18 at risk
BLOOD BILIRUBIN INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0011 affected18 at risk
BLOOD CREATININE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0012 affected18 at risk
LIPASE INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00025 affected101 at risk EG0011 affected18 at risk
LIVER FUNCTION TEST INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
LYMPHOCYTE COUNT DECREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0008 affected101 at risk EG0011 affected18 at risk
PLATELET COUNT DECREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0010 affected18 at risk
WEIGHT DECREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG00015 affected101 at risk EG0012 affected18 at risk
WEIGHT INCREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0010 affected18 at risk
WHITE BLOOD CELL COUNT DECREASED	Investigations	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0010 affected18 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00030 affected101 at risk EG0014 affected18 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0013 affected18 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0012 affected18 at risk
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0011 affected18 at risk
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0010 affected18 at risk
HYPOGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00015 affected101 at risk EG0011 affected18 at risk
HYPOMAGNESAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0013 affected18 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00014 affected101 at risk EG0014 affected18 at risk
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0011 affected18 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00036 affected101 at risk EG0011 affected18 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00019 affected101 at risk EG0014 affected18 at risk
GROIN PAIN	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0011 affected18 at risk
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0013 affected18 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00017 affected101 at risk EG0010 affected18 at risk
NECK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0012 affected18 at risk
PAIN IN JAW	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
TUMOUR PSEUDOPROGRESSION	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
AMNESIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
APHASIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0013 affected18 at risk
ATAXIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
BALANCE DISORDER	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
COORDINATION ABNORMAL	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
DIZZINESS	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00018 affected101 at risk EG0014 affected18 at risk
DYSARTHRIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
DYSGEUSIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0010 affected18 at risk
HAEMORRHAGE INTRACRANIAL	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
HEADACHE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00052 affected101 at risk EG0018 affected18 at risk
HYPOAESTHESIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
LETHARGY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
MEMORY IMPAIRMENT	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
PARAESTHESIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00011 affected101 at risk EG0011 affected18 at risk
PAROSMIA	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PERIPHERAL MOTOR NEUROPATHY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0011 affected18 at risk
PRESYNCOPE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
SEIZURE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0012 affected18 at risk
SYNCOPE	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0012 affected18 at risk
ANXIETY	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0012 affected18 at risk
CONFUSIONAL STATE	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0013 affected18 at risk
DEPRESSION	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0011 affected18 at risk
INSOMNIA	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG00023 affected101 at risk EG0015 affected18 at risk
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
NEPHRITIS	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
NOCTURIA	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
URINARY RETENTION	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
VULVOVAGINAL DRYNESS	Reproductive system and breast disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG00033 affected101 at risk EG0016 affected18 at risk
DYSPHONIA	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG00017 affected101 at risk EG0013 affected18 at risk
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
HYPOXIA	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0011 affected18 at risk
INCREASED BRONCHIAL SECRETION	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG00015 affected101 at risk EG0012 affected18 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0013 affected18 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0011 affected18 at risk
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
TACHYPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
WHEEZING	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected101 at risk EG0012 affected18 at risk
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0004 affected101 at risk EG0011 affected18 at risk
DERMATITIS ACNEIFORM	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0012 affected18 at risk
DRY SKIN	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG00010 affected101 at risk EG0013 affected18 at risk
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0011 affected18 at risk
MACULE	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
NIGHT SWEATS	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0006 affected101 at risk EG0010 affected18 at risk
ONYCHOMADESIS	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected101 at risk EG0011 affected18 at risk
PHOTOSENSITIVITY REACTION	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected101 at risk EG0011 affected18 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG00042 affected101 at risk EG0014 affected18 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG00014 affected101 at risk EG0013 affected18 at risk
RASH MACULAR	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected101 at risk EG0011 affected18 at risk
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG00042 affected101 at risk EG0015 affected18 at risk
RASH PRURITIC	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0012 affected18 at risk
SKIN HYPOPIGMENTATION	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG00010 affected101 at risk EG0011 affected18 at risk
VITILIGO	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0007 affected101 at risk EG0010 affected18 at risk
HOT FLUSH	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0005 affected101 at risk EG0011 affected18 at risk
HYPERTENSION	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG00013 affected101 at risk EG0010 affected18 at risk
HYPOTENSION	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0009 affected101 at risk EG0011 affected18 at risk

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue 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	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
BG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
BG002	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	Cohort A	Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.	29	101	50	101	97	101
EG001	Cohort B	Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.	10	18	14	18	18	18