Trial of Nivolumab vs Therapy of Investigator's Choice in... | NCT02105636

ID	Type	Description	Link
2013-003622-86	EudraCT Number

Name	Class
Ono Pharmaceutical Co., Ltd.	INDUSTRY

Label	Type	Description	Intervention Names
Arm A: Nivolumab	Experimental	Nivolumab 3mg/kg intravenous (IV) Solution for Injection every 2 weeks until disease progression	Drug: Nivolumab
Arm B: Cetuximab/Methotrexate/Docetaxel	Active Comparator	Cetuximab intravenous (IV) Solution for Injection 400 mg/m2 (first dose) then 250 mg/m2 weekly until disease progression OR Methotrexate intravenous (IV) Solution for Injection 40 or 60 mg/m2 weekly until disease progression OR Docetaxel intravenous (IV) Solution for Injection 30 or 40 mg/m2 weekly until disease progression	Drug: Cetuximab Drug: Methotrexate Drug: Docetaxel

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Drug		Arm A: Nivolumab	BMS-936558
Cetuximab

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method.	From date of randomization to date of death (Up to approximately 18 months)

Measure	Description	Time Frame
Investigator-Assessed Progression-Free Survival (PFS)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who: Die without a reported progression were considered to have progressed on the date of their death. Did not progress or die were censored on the date of their last evaluable tumor assessment. Without any on study tumor assessments and did not die were censored on their date of randomization. Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.

Eligibility Module

Eligibility Criteria

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

Inclusion Criteria:

Men and women ≥ 18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy)
Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting
Measurable disease by Computed tomography (CT) or Magnetic resonance imaging (MRI) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria

Exclusion Criteria:

Active brain metastases or leptomeningeal metastases are not allowed
Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg: mucosal melanoma) are not allowed
Subjects with active, known or suspected autoimmune disease

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

Facility	Status	City	State	ZIP	Country	Contacts
Stanford University Medical Center		Stanford	California	94305	United States
H. Lee Moffitt Cancer Center

PubMed Identifier	Type	Citation	Retractions
32583557	Derived	Yen CJ, Kiyota N, Hanai N, Takahashi S, Yokota T, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Li WSK, Ferris RL, Gillison M, Endo T, Jayaprakash V, Tahara M. Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator's choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141). Head Neck. 2020 Oct;42(10):2852-2862. doi: 10.1002/hed.26331. Epub 2020 Jun 24.
31422216

Label	URL
BMS Clinical Trial Information	View source

ID	Title	Description
FG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
FG001	Investigators Choice

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

Overall Survival (OS)

OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method.

All randomized participants

Posted

Median

95% Confidence Interval

Months

From date of randomization to date of death (Up to approximately 18 months)

ID	Title	Description
OG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
OG001	Investigators Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice

Units	Counts
Participants	OG000240 OG001121

Title

Denominators

Categories

Title	Measurements
	OG0007.49(5.49 to 9.10) OG0015.06(4.04 to 6.05)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Stratified Cox proportional hazard model. HR = Nivolumab over investigator's choice therapy (Cetuximab, Methotrexate, or Docetaxel)	Log Rank		0.0101	Log-rank Test stratified by prior treatment with cetuximab (yes, no) as entered into the Interactive Voice Response System (IVRS). For OS the boundary for statistical significance requires the p-value to be less than 0.0227.	Hazard Ratio (HR)	0.70			2-Sided	95	0.53	0.92			Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm.

Secondary

Investigator-Assessed Progression-Free Survival (PFS)

PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who:

Die without a reported progression were considered to have progressed on the date of their death.
Did not progress or die were censored on the date of their last evaluable tumor assessment.
Without any on study tumor assessments and did not die were censored on their date of randomization.
Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.

All randomized participants

Posted

Median

95% Confidence Interval

Months

From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months)

ID	Title	Description
OG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
OG001	Investigators Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice

Secondary

Investigator-Assessed Objective Response Rate (ORR)

ORR was defined as the percentage of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

All randomized participants

Posted

Number

95% Confidence Interval

Percentage of Participants

From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months)

ID	Title	Description
OG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
OG001	Investigators Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice

Post-Hoc

Overall Survival (OS) - Extended Collection

Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 10-Sep-2021)

All randomized participants

Posted

Median

95% Confidence Interval

Months

From date of randomization to date of death (Up to approximately 87 months)

ID	Title	Description
OG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
OG001	Investigators Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0014 affected111 at risk
Febrile neutropenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Leukopenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Neutropenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Thrombocytopenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Acute myocardial infarction	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Atrial fibrillation	Cardiac disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Atrial flutter	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Atrioventricular block complete	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Cardiac arrest	Cardiac disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0013 affected111 at risk
Cardiac failure	Cardiac disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Cardio-respiratory arrest	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Cardiopulmonary failure	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Cardiovascular disorder	Cardiac disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Pericarditis	Cardiac disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Supraventricular tachycardia	Cardiac disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Vertigo	Ear and labyrinth disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Hypophysitis	Endocrine disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Hypothyroidism	Endocrine disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Secondary adrenocortical insufficiency	Endocrine disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Secondary hypothyroidism	Endocrine disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Blindness unilateral	Eye disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Visual acuity reduced	Eye disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Abdominal pain	Gastrointestinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0013 affected111 at risk
Ascites	Gastrointestinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Colitis	Gastrointestinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Diarrhoea	Gastrointestinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0013 affected111 at risk
Dysphagia	Gastrointestinal disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0013 affected111 at risk
Gastric disorder	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Gastric haemorrhage	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Gastritis	Gastrointestinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Inguinal hernia	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Large intestinal obstruction	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Large intestine perforation	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Nausea	Gastrointestinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Oesophageal stenosis	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Parotid gland haemorrhage	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pneumoperitoneum	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Small intestinal obstruction	Gastrointestinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Stomatitis	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Tongue haemorrhage	Gastrointestinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Asthenia	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0012 affected111 at risk
Catheter site pain	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Chills	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Death	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Face oedema	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Fatigue	General disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0011 affected111 at risk
General physical health deterioration	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Localised oedema	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Malaise	General disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0012 affected111 at risk
Mucosal inflammation	General disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Multiple organ dysfunction syndrome	General disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Pyrexia	General disorders	24.0	Systematic Assessment	EG0005 affected236 at risk EG0014 affected111 at risk
Ulcer haemorrhage	General disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Bile duct stenosis	Hepatobiliary disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Contrast media allergy	Immune system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Eosinophilic granulomatosis with polyangiitis	Immune system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Cellulitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Clostridium difficile colitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Device related infection	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Gastrointestinal infection	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Infection	Infections and infestations	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Localised infection	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Lower respiratory tract infection	Infections and infestations	24.0	Systematic Assessment	EG0003 affected236 at risk EG0013 affected111 at risk
Lymphangitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Neutropenic sepsis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Osteomyelitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Otitis media	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Peritonitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pneumonia	Infections and infestations	24.0	Systematic Assessment	EG00017 affected236 at risk EG0015 affected111 at risk
Pneumonia bacterial	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pneumonia pseudomonal	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Purulent discharge	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Respiratory tract infection	Infections and infestations	24.0	Systematic Assessment	EG0005 affected236 at risk EG0011 affected111 at risk
Sepsis	Infections and infestations	24.0	Systematic Assessment	EG0006 affected236 at risk EG0014 affected111 at risk
Septic shock	Infections and infestations	24.0	Systematic Assessment	EG0003 affected236 at risk EG0011 affected111 at risk
Sinusitis	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Skin infection	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Systemic infection	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Tracheitis	Infections and infestations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Upper respiratory tract infection	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Urinary tract infection	Infections and infestations	24.0	Systematic Assessment	EG0004 affected236 at risk EG0010 affected111 at risk
Vascular device infection	Infections and infestations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Wound infection	Infections and infestations	24.0	Systematic Assessment	EG0003 affected236 at risk EG0012 affected111 at risk
Humerus fracture	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Infusion related reaction	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0003 affected236 at risk EG0011 affected111 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0002 affected236 at risk EG0011 affected111 at risk
Procedural haemorrhage	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Shunt thrombosis	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Vascular pseudoaneurysm ruptured	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Wound	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Wound haemorrhage	Injury, poisoning and procedural complications	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Blood alkaline phosphatase increased	Investigations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Blood bilirubin increased	Investigations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
General physical condition abnormal	Investigations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Liver function test abnormal	Investigations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Liver function test increased	Investigations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Platelet count decreased	Investigations	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Transaminases increased	Investigations	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Decreased appetite	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG0011 affected111 at risk
Dehydration	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG0011 affected111 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Failure to thrive	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Hyperamylasaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Hypercalcaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0011 affected111 at risk
Hyperglycaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Hypernatraemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Hyponatraemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG0011 affected111 at risk
Hypophagia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Hypophosphataemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Malnutrition	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0010 affected111 at risk
Back pain	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Fistula	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Head and neck cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG00094 affected236 at risk EG00155 affected111 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0002 affected236 at risk EG0013 affected111 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG0001 affected236 at risk EG0014 affected111 at risk
Cerebral ischaemia	Nervous system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Cerebrovascular accident	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Dizziness	Nervous system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0012 affected111 at risk
Encephalopathy	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Focal dyscognitive seizures	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Headache	Nervous system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Hydrocephalus	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Ischaemic stroke	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Neuralgia	Nervous system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Radiculopathy	Nervous system disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Speech disorder	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Syncope	Nervous system disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Device leakage	Product Issues	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Device occlusion	Product Issues	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Agoraphobia	Psychiatric disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Anxiety	Psychiatric disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Confusional state	Psychiatric disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Delirium	Psychiatric disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Suicide attempt	Psychiatric disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Acute kidney injury	Renal and urinary disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0011 affected111 at risk
Bronchopneumopathy	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Cough	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG00011 affected236 at risk EG0012 affected111 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0012 affected111 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0011 affected111 at risk
Laryngeal stenosis	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0013 affected111 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG00010 affected236 at risk EG0014 affected111 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0013 affected111 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0005 affected236 at risk EG0011 affected111 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Angioedema	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Dermatomyositis	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Skin mass	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Skin toxicity	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Deep vein thrombosis	Vascular disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Haematoma	Vascular disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Haemorrhage	Vascular disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0010 affected111 at risk
Hypertensive urgency	Vascular disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Hypotension	Vascular disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Hypovolaemic shock	Vascular disorders	24.0	Systematic Assessment	EG0000 affected236 at risk EG0011 affected111 at risk
Shock haemorrhagic	Vascular disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Superior vena cava syndrome	Vascular disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk
Venous thrombosis	Vascular disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0010 affected111 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG00053 affected236 at risk EG00142 affected111 at risk
Neutropenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0002 affected236 at risk EG0019 affected111 at risk
Thrombocytopenia	Blood and lymphatic system disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG0016 affected111 at risk
Tachycardia	Cardiac disorders	24.0	Systematic Assessment	EG0007 affected236 at risk EG0017 affected111 at risk
Hypothyroidism	Endocrine disorders	24.0	Systematic Assessment	EG00021 affected236 at risk EG0017 affected111 at risk
Lacrimation increased	Eye disorders	24.0	Systematic Assessment	EG0001 affected236 at risk EG0016 affected111 at risk
Constipation	Gastrointestinal disorders	24.0	Systematic Assessment	EG00043 affected236 at risk EG00121 affected111 at risk
Diarrhoea	Gastrointestinal disorders	24.0	Systematic Assessment	EG00047 affected236 at risk EG00127 affected111 at risk
Dry mouth	Gastrointestinal disorders	24.0	Systematic Assessment	EG0008 affected236 at risk EG0018 affected111 at risk
Dyspepsia	Gastrointestinal disorders	24.0	Systematic Assessment	EG0007 affected236 at risk EG0016 affected111 at risk
Dysphagia	Gastrointestinal disorders	24.0	Systematic Assessment	EG00030 affected236 at risk EG00117 affected111 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0018 affected111 at risk
Nausea	Gastrointestinal disorders	24.0	Systematic Assessment	EG00055 affected236 at risk EG00137 affected111 at risk
Stomatitis	Gastrointestinal disorders	24.0	Systematic Assessment	EG00014 affected236 at risk EG00112 affected111 at risk
Vomiting	Gastrointestinal disorders	24.0	Systematic Assessment	EG00028 affected236 at risk EG00116 affected111 at risk
Asthenia	General disorders	24.0	Systematic Assessment	EG00027 affected236 at risk EG00124 affected111 at risk
Face oedema	General disorders	24.0	Systematic Assessment	EG00011 affected236 at risk EG0018 affected111 at risk
Fatigue	General disorders	24.0	Systematic Assessment	EG00067 affected236 at risk EG00137 affected111 at risk
Mucosal inflammation	General disorders	24.0	Systematic Assessment	EG00011 affected236 at risk EG00119 affected111 at risk
Oedema peripheral	General disorders	24.0	Systematic Assessment	EG00019 affected236 at risk EG0015 affected111 at risk
Pyrexia	General disorders	24.0	Systematic Assessment	EG00037 affected236 at risk EG00116 affected111 at risk
Oral candidiasis	Infections and infestations	24.0	Systematic Assessment	EG00011 affected236 at risk EG0016 affected111 at risk
Pneumonia	Infections and infestations	24.0	Systematic Assessment	EG00016 affected236 at risk EG0015 affected111 at risk
Respiratory tract infection	Infections and infestations	24.0	Systematic Assessment	EG0006 affected236 at risk EG0016 affected111 at risk
Alanine aminotransferase increased	Investigations	24.0	Systematic Assessment	EG0009 affected236 at risk EG0016 affected111 at risk
Aspartate aminotransferase increased	Investigations	24.0	Systematic Assessment	EG00014 affected236 at risk EG0016 affected111 at risk
Blood alkaline phosphatase increased	Investigations	24.0	Systematic Assessment	EG00018 affected236 at risk EG0013 affected111 at risk
Lipase increased	Investigations	24.0	Systematic Assessment	EG00013 affected236 at risk EG0012 affected111 at risk
Lymphocyte count decreased	Investigations	24.0	Systematic Assessment	EG0008 affected236 at risk EG0016 affected111 at risk
Weight decreased	Investigations	24.0	Systematic Assessment	EG00035 affected236 at risk EG00119 affected111 at risk
White blood cell count decreased	Investigations	24.0	Systematic Assessment	EG0003 affected236 at risk EG0018 affected111 at risk
Decreased appetite	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00046 affected236 at risk EG00121 affected111 at risk
Hypercalcaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00017 affected236 at risk EG0018 affected111 at risk
Hyperglycaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00016 affected236 at risk EG0019 affected111 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00012 affected236 at risk EG0014 affected111 at risk
Hypokalaemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00011 affected236 at risk EG0017 affected111 at risk
Hyponatraemia	Metabolism and nutrition disorders	24.0	Systematic Assessment	EG00025 affected236 at risk EG00115 affected111 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG00019 affected236 at risk EG0012 affected111 at risk
Back pain	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG00017 affected236 at risk EG0010 affected111 at risk
Neck pain	Musculoskeletal and connective tissue disorders	24.0	Systematic Assessment	EG00017 affected236 at risk EG0019 affected111 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.0	Systematic Assessment	EG00013 affected236 at risk EG0018 affected111 at risk
Dizziness	Nervous system disorders	24.0	Systematic Assessment	EG0009 affected236 at risk EG0017 affected111 at risk
Headache	Nervous system disorders	24.0	Systematic Assessment	EG00023 affected236 at risk EG0014 affected111 at risk
Neuropathy peripheral	Nervous system disorders	24.0	Systematic Assessment	EG0006 affected236 at risk EG0019 affected111 at risk
Paraesthesia	Nervous system disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG0016 affected111 at risk
Anxiety	Psychiatric disorders	24.0	Systematic Assessment	EG0009 affected236 at risk EG0019 affected111 at risk
Depression	Psychiatric disorders	24.0	Systematic Assessment	EG00012 affected236 at risk EG0013 affected111 at risk
Insomnia	Psychiatric disorders	24.0	Systematic Assessment	EG00013 affected236 at risk EG0017 affected111 at risk
Cough	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG00037 affected236 at risk EG00113 affected111 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG00032 affected236 at risk EG00112 affected111 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0005 affected236 at risk EG00111 affected111 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG0005 affected236 at risk EG0016 affected111 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	24.0	Systematic Assessment	EG00014 affected236 at risk EG0012 affected111 at risk
Alopecia	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0004 affected236 at risk EG00116 affected111 at risk
Dry skin	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG00014 affected236 at risk EG00112 affected111 at risk
Erythema	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG0003 affected236 at risk EG0016 affected111 at risk
Pruritus	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG00023 affected236 at risk EG0011 affected111 at risk
Rash	Skin and subcutaneous tissue disorders	24.0	Systematic Assessment	EG00022 affected236 at risk EG0016 affected111 at risk
Hypertension	Vascular disorders	24.0	Systematic Assessment	EG00016 affected236 at risk EG0014 affected111 at risk

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D009371	Neoplasms by Site

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
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Nivolumab 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
BG001	Investigators Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice
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 3mg/kg	Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression	220	240	165	236	210	236
EG001	Investigator Choice	Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m^2) for the first dose followed that a doses of 250 mg/m^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice	119	121	87	111	108	111

ID	Term
D000077594	Nivolumab
D000068818	Cetuximab
D008727	Methotrexate
D000077143	Docetaxel