Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared... | NCT01927419

ID	Type	Description	Link
2013-002018-11	EudraCT Number

Label	Type	Description	Intervention Names
Nivolumab + Ipilimumab	Experimental	Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.	Drug: Nivolumab Drug: Ipilimumab
Placebo + Ipilimumab	Experimental	Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.	Drug: Ipilimumab Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Drug		Nivolumab + Ipilimumab	Opdivo, BMS-936558
Ipilimumab

Measure	Description	Time Frame
Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants	Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria. CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm). PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.	From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)

Measure	Description	Time Frame
Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants	PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment. PFS values are based on Kaplan-Meier Estimates.

Eligibility Module

Eligibility Criteria

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

Key Inclusion Criteria:

Eastern Cooperative Oncology Group performance status of 0 or 1
Histologically confirmed unresectable Stage III or Stage IV melanoma
No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.

Key Exclusion Criteria:

Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
Ocular melanoma
Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

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

Facility	Status	City	State	ZIP	Country	Contacts
San Francisco Oncology Associates		San Francisco	California	94115	United States
Orlando Health Inc

PubMed Identifier	Type	Citation	Retractions
39504507	Derived	Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.
34855329

Label	URL
BMS Clinical Trial Information	View source

ID	Title	Description
FG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants

Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.

CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).

PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

All randomized BRAF wild-type participants .

Posted

Number

95% Confidence Interval

Percentage of participants

From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)

ID	Title	Description
OG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
OG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Units	Counts
Participants	OG00073 OG00137

Title

Denominators

Categories

Title	Measurements
	OG00060.3(48.1 to 71.5) OG00110.8(3.0 to 25.4)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact				Mean Difference (Final Values)	49.5			2-Sided	95	31.4	61.8			Difference of ORR		Superiority		Exact 95% CI for difference in ORR uses Newcombe's method
OG000 OG001		Fisher Exact

Secondary

Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants

PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment.

PFS values are based on Kaplan-Meier Estimates.

All randomized BRAF wild-type participants

Posted

Median

95% Confidence Interval

Months

From randomization to progression or death (up to approximately 88 months)

ID	Title	Description
OG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
OG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Secondary

Objective Response Rate (ORR) - BRAF Mutant Participants

CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).

PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

All randomized BRAF mutant participants

Posted

Number

95% Confidence Interval

Percentage of participants

From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)

ID	Title	Description
OG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
OG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Secondary

Progression-Free Survival (PFS) - BRAF Mutant Participants

PFS values are based on Kaplan-Meier Estimates.

All randomized BRAF mutant participants

Posted

Median

95% Confidence Interval

Months

From randomization to progression or death (up to approximately 88 months)

ID	Title	Description
OG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
OG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score

The EORTC QLQ-C30 version 3 is a questionnaire developed to assess the QOL of cancer patients. The questionnaire is a 30-item tool, and it comprises 6 functional subscales (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as 9 symptom subscales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).

Scores for each subscale range from 0 to 100. For the 6 functional subscales, a higher score represents a better level of functioning/health status. For the 9 symptom subscales, a lower score represents a better outcome (low level of symptomatology).

Scores for the 15 subscales are presented individually.

All randomized participants with available measurements at baseline and week 25

Posted

Mean

Standard Deviation

Score on a scale

From Baseline (prior to start of study treatment) to Week 25 after first dose

ID	Title	Description
OG000	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
OG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Haemolysis	Blood and lymphatic system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Leukocytosis	Blood and lymphatic system disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Thrombocytopenia	Blood and lymphatic system disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Angina pectoris	Cardiac disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Atrial fibrillation	Cardiac disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0011 affected46 at risk
Cardiac failure	Cardiac disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Myocardial infarction	Cardiac disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Supraventricular tachycardia	Cardiac disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Ventricular arrhythmia	Cardiac disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Adrenal insufficiency	Endocrine disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Adrenocortical insufficiency acute	Endocrine disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Autoimmune thyroiditis	Endocrine disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Endocrine disorder	Endocrine disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Hypercalcaemia of malignancy	Endocrine disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Hypophysitis	Endocrine disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0011 affected46 at risk
Hypopituitarism	Endocrine disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Abdominal pain	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Abdominal pain lower	Gastrointestinal disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Ascites	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Autoimmune colitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0012 affected46 at risk
Colitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG00013 affected94 at risk EG0012 affected46 at risk
Constipation	Gastrointestinal disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Diarrhoea	Gastrointestinal disorders	23.1	Systematic Assessment	EG00010 affected94 at risk EG0015 affected46 at risk
Diarrhoea haemorrhagic	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Enterocolitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Immune-mediated enterocolitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Large intestine perforation	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Nausea	Gastrointestinal disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0012 affected46 at risk
Oesophageal pain	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Pancreatitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Small intestinal obstruction	Gastrointestinal disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Vomiting	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0012 affected46 at risk
Chills	General disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Generalised oedema	General disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Non-cardiac chest pain	General disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Pain	General disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Pyrexia	General disorders	23.1	Systematic Assessment	EG0006 affected94 at risk EG0014 affected46 at risk
Hepatitis	Hepatobiliary disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Hepatocellular injury	Hepatobiliary disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Abdominal abscess	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Abscess	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Cellulitis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Diverticulitis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Encephalitis	Infections and infestations	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Enterococcal bacteraemia	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Epididymitis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Gastroenteritis viral	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Necrotising fasciitis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Oral candidiasis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Periorbital cellulitis	Infections and infestations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Pneumonia	Infections and infestations	23.1	Systematic Assessment	EG0004 affected94 at risk EG0013 affected46 at risk
Sepsis	Infections and infestations	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Septic shock	Infections and infestations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Alanine aminotransferase increased	Investigations	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Amylase increased	Investigations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Aspartate aminotransferase increased	Investigations	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Blood creatinine increased	Investigations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Lipase increased	Investigations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0011 affected46 at risk
Transaminases increased	Investigations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Dehydration	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0011 affected46 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Hypercalcaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Hyperglycaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Hyperkalaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Hyponatraemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0010 affected46 at risk
Hypophosphataemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Back pain	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Myalgia	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	23.1	Systematic Assessment	EG00010 affected94 at risk EG0018 affected46 at risk
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	23.1	Systematic Assessment	EG0001 affected94 at risk EG0011 affected46 at risk
Dizziness	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Embolic stroke	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Guillain-Barre syndrome	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Haemorrhagic stroke	Nervous system disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Meningoradiculitis	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Neuralgia	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Seizure	Nervous system disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0012 affected46 at risk
Spinal cord compression	Nervous system disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Syncope	Nervous system disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Tremor	Nervous system disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Acute kidney injury	Renal and urinary disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Haematuria	Renal and urinary disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Urinary tract obstruction	Renal and urinary disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0011 affected46 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0012 affected46 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0011 affected46 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0007 affected94 at risk EG0012 affected46 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0011 affected46 at risk
Rash	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0010 affected46 at risk
Deep vein thrombosis	Vascular disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0010 affected46 at risk
Embolism	Vascular disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Hypertension	Vascular disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0011 affected46 at risk
Hypotension	Vascular disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0012 affected46 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	23.1	Systematic Assessment	EG00024 affected94 at risk EG00115 affected46 at risk
Atrial fibrillation	Cardiac disorders	23.1	Systematic Assessment	EG0006 affected94 at risk EG0013 affected46 at risk
Sinus tachycardia	Cardiac disorders	23.1	Systematic Assessment	EG0004 affected94 at risk EG0013 affected46 at risk
Tachycardia	Cardiac disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0015 affected46 at risk
Ear pain	Ear and labyrinth disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0011 affected46 at risk
Adrenal insufficiency	Endocrine disorders	23.1	Systematic Assessment	EG0007 affected94 at risk EG0013 affected46 at risk
Hypophysitis	Endocrine disorders	23.1	Systematic Assessment	EG00010 affected94 at risk EG0012 affected46 at risk
Hypothyroidism	Endocrine disorders	23.1	Systematic Assessment	EG00018 affected94 at risk EG0017 affected46 at risk
Vision blurred	Eye disorders	23.1	Systematic Assessment	EG00015 affected94 at risk EG0010 affected46 at risk
Abdominal discomfort	Gastrointestinal disorders	23.1	Systematic Assessment	EG0004 affected94 at risk EG0013 affected46 at risk
Abdominal distension	Gastrointestinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0013 affected46 at risk
Abdominal pain	Gastrointestinal disorders	23.1	Systematic Assessment	EG00020 affected94 at risk EG00112 affected46 at risk
Abdominal pain upper	Gastrointestinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0013 affected46 at risk
Colitis	Gastrointestinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0014 affected46 at risk
Constipation	Gastrointestinal disorders	23.1	Systematic Assessment	EG00032 affected94 at risk EG00114 affected46 at risk
Diarrhoea	Gastrointestinal disorders	23.1	Systematic Assessment	EG00054 affected94 at risk EG00124 affected46 at risk
Dry mouth	Gastrointestinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0016 affected46 at risk
Dyspepsia	Gastrointestinal disorders	23.1	Systematic Assessment	EG0007 affected94 at risk EG0013 affected46 at risk
Flatulence	Gastrointestinal disorders	23.1	Systematic Assessment	EG0004 affected94 at risk EG0014 affected46 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0012 affected46 at risk
Nausea	Gastrointestinal disorders	23.1	Systematic Assessment	EG00040 affected94 at risk EG00125 affected46 at risk
Rectal haemorrhage	Gastrointestinal disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0014 affected46 at risk
Vomiting	Gastrointestinal disorders	23.1	Systematic Assessment	EG00029 affected94 at risk EG00111 affected46 at risk
Asthenia	General disorders	23.1	Systematic Assessment	EG00017 affected94 at risk EG00111 affected46 at risk
Chills	General disorders	23.1	Systematic Assessment	EG00021 affected94 at risk EG0018 affected46 at risk
Fatigue	General disorders	23.1	Systematic Assessment	EG00057 affected94 at risk EG00134 affected46 at risk
Influenza like illness	General disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0016 affected46 at risk
Malaise	General disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0013 affected46 at risk
Mucosal inflammation	General disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0015 affected46 at risk
Non-cardiac chest pain	General disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0014 affected46 at risk
Oedema peripheral	General disorders	23.1	Systematic Assessment	EG00026 affected94 at risk EG00110 affected46 at risk
Pain	General disorders	23.1	Systematic Assessment	EG00014 affected94 at risk EG00110 affected46 at risk
Peripheral swelling	General disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0013 affected46 at risk
Pyrexia	General disorders	23.1	Systematic Assessment	EG00032 affected94 at risk EG00117 affected46 at risk
Pneumonia	Infections and infestations	23.1	Systematic Assessment	EG0002 affected94 at risk EG0015 affected46 at risk
Upper respiratory tract infection	Infections and infestations	23.1	Systematic Assessment	EG0007 affected94 at risk EG0015 affected46 at risk
Urinary tract infection	Infections and infestations	23.1	Systematic Assessment	EG0009 affected94 at risk EG0012 affected46 at risk
Alanine aminotransferase increased	Investigations	23.1	Systematic Assessment	EG00030 affected94 at risk EG0017 affected46 at risk
Amylase increased	Investigations	23.1	Systematic Assessment	EG00014 affected94 at risk EG0013 affected46 at risk
Aspartate aminotransferase increased	Investigations	23.1	Systematic Assessment	EG00031 affected94 at risk EG0017 affected46 at risk
Blood alkaline phosphatase increased	Investigations	23.1	Systematic Assessment	EG00013 affected94 at risk EG0017 affected46 at risk
Blood bilirubin increased	Investigations	23.1	Systematic Assessment	EG00012 affected94 at risk EG0011 affected46 at risk
Blood creatinine increased	Investigations	23.1	Systematic Assessment	EG00010 affected94 at risk EG0014 affected46 at risk
Blood thyroid stimulating hormone decreased	Investigations	23.1	Systematic Assessment	EG0007 affected94 at risk EG0011 affected46 at risk
Blood thyroid stimulating hormone increased	Investigations	23.1	Systematic Assessment	EG0008 affected94 at risk EG0010 affected46 at risk
Lipase increased	Investigations	23.1	Systematic Assessment	EG00022 affected94 at risk EG0016 affected46 at risk
Platelet count decreased	Investigations	23.1	Systematic Assessment	EG0005 affected94 at risk EG0010 affected46 at risk
Weight decreased	Investigations	23.1	Systematic Assessment	EG00016 affected94 at risk EG0012 affected46 at risk
Weight increased	Investigations	23.1	Systematic Assessment	EG0005 affected94 at risk EG0013 affected46 at risk
Decreased appetite	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00026 affected94 at risk EG00117 affected46 at risk
Dehydration	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00022 affected94 at risk EG0014 affected46 at risk
Hyperglycaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00013 affected94 at risk EG0013 affected46 at risk
Hyperkalaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0008 affected94 at risk EG0012 affected46 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00011 affected94 at risk EG0016 affected46 at risk
Hypocalcaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0012 affected46 at risk
Hypokalaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00015 affected94 at risk EG0015 affected46 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00011 affected94 at risk EG0013 affected46 at risk
Hyponatraemia	Metabolism and nutrition disorders	23.1	Systematic Assessment	EG00022 affected94 at risk EG0016 affected46 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG00026 affected94 at risk EG00111 affected46 at risk
Back pain	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG00019 affected94 at risk EG0017 affected46 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG0006 affected94 at risk EG0012 affected46 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG00012 affected94 at risk EG0012 affected46 at risk
Myalgia	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG00014 affected94 at risk EG00113 affected46 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	23.1	Systematic Assessment	EG00010 affected94 at risk EG0019 affected46 at risk
Dizziness	Nervous system disorders	23.1	Systematic Assessment	EG00017 affected94 at risk EG0015 affected46 at risk
Dysgeusia	Nervous system disorders	23.1	Systematic Assessment	EG0006 affected94 at risk EG0011 affected46 at risk
Headache	Nervous system disorders	23.1	Systematic Assessment	EG00035 affected94 at risk EG00111 affected46 at risk
Paraesthesia	Nervous system disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0010 affected46 at risk
Peripheral sensory neuropathy	Nervous system disorders	23.1	Systematic Assessment	EG0004 affected94 at risk EG0014 affected46 at risk
Taste disorder	Nervous system disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0010 affected46 at risk
Anxiety	Psychiatric disorders	23.1	Systematic Assessment	EG0007 affected94 at risk EG0014 affected46 at risk
Depression	Psychiatric disorders	23.1	Systematic Assessment	EG0004 affected94 at risk EG0014 affected46 at risk
Insomnia	Psychiatric disorders	23.1	Systematic Assessment	EG00020 affected94 at risk EG00111 affected46 at risk
Pollakiuria	Renal and urinary disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0011 affected46 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	23.1	Systematic Assessment	EG0000 affected94 at risk EG0013 affected46 at risk
Cough	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG00030 affected94 at risk EG00120 affected46 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0007 affected94 at risk EG0013 affected46 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG00028 affected94 at risk EG00114 affected46 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0011 affected46 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0015 affected46 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0015 affected46 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0014 affected46 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0012 affected46 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0014 affected46 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0013 affected46 at risk
Dry skin	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0009 affected94 at risk EG0015 affected46 at risk
Erythema	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG00010 affected94 at risk EG0011 affected46 at risk
Night sweats	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0008 affected94 at risk EG0011 affected46 at risk
Pruritus	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG00047 affected94 at risk EG00117 affected46 at risk
Rash	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG00045 affected94 at risk EG00117 affected46 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0002 affected94 at risk EG0014 affected46 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG00016 affected94 at risk EG0018 affected46 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0003 affected94 at risk EG0014 affected46 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0010 affected46 at risk
Vitiligo	Skin and subcutaneous tissue disorders	23.1	Systematic Assessment	EG00011 affected94 at risk EG0014 affected46 at risk
Flushing	Vascular disorders	23.1	Systematic Assessment	EG0005 affected94 at risk EG0011 affected46 at risk
Hot flush	Vascular disorders	23.1	Systematic Assessment	EG0001 affected94 at risk EG0013 affected46 at risk
Hypertension	Vascular disorders	23.1	Systematic Assessment	EG00012 affected94 at risk EG0014 affected46 at risk
Hypotension	Vascular disorders	23.1	Systematic Assessment	EG00011 affected94 at risk EG0015 affected46 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	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
BG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
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	Nivolumab + Ipilimumab	Participants received 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.	44	94	69	94	90	94
EG001	Ipilimumab	Participants received placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.	29	46	27	46	45	46