Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)

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ClinicalTrials.gov Identifier: NCT02105636

Recruitment Status : Completed

First Posted : April 7, 2014

Results First Posted : January 11, 2017

Last Update Posted : October 5, 2022

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Sponsor:

Collaborator:

Ono Pharmaceutical Co. Ltd

Information provided by (Responsible Party):

Bristol-Myers Squibb

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Squamous Cell Carcinoma of the Head and Neck
Interventions	Drug: Nivolumab Drug: Cetuximab Drug: Methotrexate Drug: Docetaxel
Enrollment	361

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Nivolumab 3mg/kg	Investigators Choice
Arm/Group Description	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description	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.	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
Period Title: Pre-Treatment
Started ^[1]	240	121
Completed ^[2]	236	111
Not Completed	4	10
Reason Not Completed
Disease Progression	1	0
Participant request to discontinue study treatment	1	2
Participant withdrew consent	0	6
Participant no longer meets study criteria	2	2
[1] Started = Randomized [2] Completed = Entering treatment
Period Title: Treatment
Started	236	111
Completed	1	0
Not Completed	235	111
Reason Not Completed
Study Drug Toxicity	14	10
Adverse event unrelated to study drug	19	3
Participant request to discontinue study treatment	8	6
Participant withdrew consent	5	1
Lost to Follow-up	1	0
Maximum Clinical Benefit	1	3
Poor/Non-compliance	0	1
Participant no longer meets study criteria	1	0
Other reasons	1	0
Disease Progression	185	87

Baseline Characteristics

Arm/Group Title		Nivolumab 3mg/kg	Investigators Choice	Total
Arm/Group Description		Nivolumab was provided at a dose of...	Participants were provided a dose o...	Total of all reporting groups
Arm/Group Description		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.	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	Total of all reporting groups
Overall Number of Baseline Participants		240	121	361
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	240 participants	121 participants	361 participants
		59.0 (10.15)	59.4 (11.00)	59.1 (10.43)
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	240 participants	121 participants	361 participants
< 65 years		172	76	248
>=65 and <75 years		56	39	95
>=75 years		12	6	18
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	240 participants	121 participants	361 participants
	Female	43 17.9%	18 14.9%	61 16.9%
	Male	197 82.1%	103 85.1%	300 83.1%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	240 participants	121 participants	361 participants
White		196	104	300
Black or African American		10	3	13
Asian		29	14	43
Other		5	0	5
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	240 participants	121 participants	361 participants
Hispanic/Latino		9	4	13
Not Hispanic/Latino		132	60	192
Not Reported		99	57	156

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to the date of death fro...
Description	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.
Time Frame	From date of randomization to date of death (Up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3mg/kg	Investigators Choice
Arm/Group Description:	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description:	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.	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
Overall Number of Participants Analyzed	240	121
Median (95% Confidence Interval) Unit of Measure: Months
	7.49 (5.49 to 9.10)	5.06 (4.04 to 6.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3mg/kg, Investigators Choice
	Comments	Stratified Cox proportional hazard model. HR = Nivolumab over investigator's choice therapy (Cetuximab, Methotrexate, or Docetaxel)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0101
	Comments	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.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95% 0.53 to 0.92
	Estimation Comments	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.

2.Secondary Outcome


Title	Investigator-Assessed Progression-Free Survival (PFS)
Description	PFS was defined as the time between the date of randomization and the ...
Description	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.
Time Frame	From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3mg/kg	Investigators Choice
Arm/Group Description:	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description:	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.	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
Overall Number of Participants Analyzed	240	121
Median (95% Confidence Interval) Unit of Measure: Months
	2.04 (1.91 to 2.14)	2.33 (1.94 to 3.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3mg/kg, Investigators Choice
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.68 to 1.10
	Estimation Comments	Number of responders (CR +PR) over number of participants

3.Secondary Outcome


Title	Investigator-Assessed Objective Response Rate (ORR)
Description	ORR was defined as the percentage of randomized participants who achie...
Description	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.
Time Frame	From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3mg/kg	Investigators Choice
Arm/Group Description:	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description:	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.	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
Overall Number of Participants Analyzed	240	121
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
	13.3 (9.3 to 18.3)	5.8 (2.4 to 11.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3mg/kg, Investigators Choice
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in ORR
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95% 1.5 to 13.6
	Estimation Comments	Stratum adjusted difference in response rates (Nivolumab - Investigators Choice) based on the Cochran-Mantel-Haenszel method of weighting.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3mg/kg, Investigators Choice
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	CMH Estimate of Common Odds Ratio
	Estimated Value	2.49
	Confidence Interval	(2-Sided) 95% 1.07 to 5.82
	Estimation Comments	Stratified by Prior Cetuximab (yes, no) as recorded in the IVRS. Stratum adjusted odds ratio (Nivolumab - Investigators Choice) using Mantel-Haenszel Method.

4.Post-Hoc Outcome


Title	Overall Survival (OS) - Extended Collection
Description	OS was defined as the time from randomization to the date of death fro...
Description	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. 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)
Time Frame	From date of randomization to date of death (Up to approximately 87 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3mg/kg	Investigators Choice
Arm/Group Description:	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description:	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.	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
Overall Number of Participants Analyzed	240	121
Median (95% Confidence Interval) Unit of Measure: Months
	7.72 (5.68 to 8.74)	5.06 (4.04 to 6.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3mg/kg, Investigators Choice
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95% 0.54 to 0.85
	Estimation Comments	Stratified Cox proportional hazards model. Hazard ratio of nivolumab to investigator's choice therapy.

Adverse Events

Time Frame	Adverse Events and Serious Adverse Events were monitored from first dose to 100 days post last dose (Up to a maximum of approximately 70 months). Participants were assessed for All Cause Mortality from their date of randomization until the study was completed (up to approximately 87 months)
Adverse Event Reporting Description	The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication

Arm/Group Title	Nivolumab 3mg/kg	Investigator Choice
Arm/Group Description	Nivolumab was provided at a dose of...	Participants were provided a dose o...
Arm/Group Description	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	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
All-Cause Mortality
	Nivolumab 3mg/kg	Investigator Choice
	Affected / at Risk (%)	Affected / at Risk (%)
Total	220/240 (91.67%)	119/121 (98.35%)
Serious Adverse Events Serious Adverse Events
	Nivolumab 3mg/kg	Investigator Choice
	Affected / at Risk (%)	Affected / at Risk (%)
Total	165/236 (69.92%)	87/111 (78.38%)
Blood and lymphatic system disorders
Anaemia ^† 1	2/236 (0.85%)	4/111 (3.60%)
Febrile neutropenia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Leukopenia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Neutropenia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Thrombocytopenia ^† 1	2/236 (0.85%)	0/111 (0.00%)
Cardiac disorders
Acute myocardial infarction ^† 1	1/236 (0.42%)	0/111 (0.00%)
Atrial fibrillation ^† 1	0/236 (0.00%)	1/111 (0.90%)
Atrial flutter ^† 1	1/236 (0.42%)	1/111 (0.90%)
Atrioventricular block complete ^† 1	1/236 (0.42%)	0/111 (0.00%)
Cardiac arrest ^† 1	0/236 (0.00%)	3/111 (2.70%)
Cardiac failure ^† 1	2/236 (0.85%)	0/111 (0.00%)
Cardio-respiratory arrest ^† 1	1/236 (0.42%)	0/111 (0.00%)
Cardiopulmonary failure ^† 1	1/236 (0.42%)	0/111 (0.00%)
Cardiovascular disorder ^† 1	0/236 (0.00%)	1/111 (0.90%)
Pericarditis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Supraventricular tachycardia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula ^† 1	0/236 (0.00%)	1/111 (0.90%)
Ear and labyrinth disorders
Vertigo ^† 1	0/236 (0.00%)	1/111 (0.90%)
Endocrine disorders
Hypophysitis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hypothyroidism ^† 1	1/236 (0.42%)	0/111 (0.00%)
Secondary adrenocortical insufficiency ^† 1	1/236 (0.42%)	0/111 (0.00%)
Secondary hypothyroidism ^† 1	1/236 (0.42%)	0/111 (0.00%)
Eye disorders
Blindness unilateral ^† 1	1/236 (0.42%)	0/111 (0.00%)
Visual acuity reduced ^† 1	0/236 (0.00%)	1/111 (0.90%)
Gastrointestinal disorders
Abdominal pain ^† 1	2/236 (0.85%)	3/111 (2.70%)
Ascites ^† 1	0/236 (0.00%)	1/111 (0.90%)
Colitis ^† 1	0/236 (0.00%)	1/111 (0.90%)
Diarrhoea ^† 1	2/236 (0.85%)	3/111 (2.70%)
Dysphagia ^† 1	3/236 (1.27%)	3/111 (2.70%)
Gastric disorder ^† 1	1/236 (0.42%)	0/111 (0.00%)
Gastric haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Gastritis ^† 1	0/236 (0.00%)	1/111 (0.90%)
Inguinal hernia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Large intestinal obstruction ^† 1	1/236 (0.42%)	0/111 (0.00%)
Large intestine perforation ^† 1	1/236 (0.42%)	0/111 (0.00%)
Nausea ^† 1	0/236 (0.00%)	1/111 (0.90%)
Oesophageal stenosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Parotid gland haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pneumoperitoneum ^† 1	1/236 (0.42%)	0/111 (0.00%)
Small intestinal obstruction ^† 1	0/236 (0.00%)	1/111 (0.90%)
Stomatitis ^† 1	1/236 (0.42%)	1/111 (0.90%)
Tongue haemorrhage ^† 1	2/236 (0.85%)	0/111 (0.00%)
Upper gastrointestinal haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
General disorders
Asthenia ^† 1	1/236 (0.42%)	2/111 (1.80%)
Catheter site pain ^† 1	1/236 (0.42%)	0/111 (0.00%)
Chills ^† 1	1/236 (0.42%)	1/111 (0.90%)
Death ^† 1	1/236 (0.42%)	0/111 (0.00%)
Face oedema ^† 1	1/236 (0.42%)	1/111 (0.90%)
Fatigue ^† 1	3/236 (1.27%)	1/111 (0.90%)
General physical health deterioration ^† 1	1/236 (0.42%)	0/111 (0.00%)
Localised oedema ^† 1	1/236 (0.42%)	0/111 (0.00%)
Malaise ^† 1	0/236 (0.00%)	2/111 (1.80%)
Mucosal inflammation ^† 1	0/236 (0.00%)	1/111 (0.90%)
Multiple organ dysfunction syndrome ^† 1	0/236 (0.00%)	1/111 (0.90%)
Pyrexia ^† 1	5/236 (2.12%)	4/111 (3.60%)
Ulcer haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hepatobiliary disorders
Bile duct stenosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Immune system disorders
Contrast media allergy ^† 1	0/236 (0.00%)	1/111 (0.90%)
Eosinophilic granulomatosis with polyangiitis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Infections and infestations
Cellulitis ^† 1	1/236 (0.42%)	1/111 (0.90%)
Clostridium difficile colitis ^† 1	1/236 (0.42%)	1/111 (0.90%)
Device related infection ^† 1	1/236 (0.42%)	1/111 (0.90%)
Gastrointestinal infection ^† 1	0/236 (0.00%)	1/111 (0.90%)
Infection ^† 1	2/236 (0.85%)	0/111 (0.00%)
Localised infection ^† 1	1/236 (0.42%)	1/111 (0.90%)
Lower respiratory tract infection ^† 1	3/236 (1.27%)	3/111 (2.70%)
Lymphangitis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Neutropenic sepsis ^† 1	1/236 (0.42%)	1/111 (0.90%)
Osteomyelitis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Otitis media ^† 1	1/236 (0.42%)	0/111 (0.00%)
Peritonitis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pneumocystis jirovecii pneumonia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pneumonia ^† 1	17/236 (7.20%)	5/111 (4.50%)
Pneumonia bacterial ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pneumonia pseudomonal ^† 1	0/236 (0.00%)	1/111 (0.90%)
Purulent discharge ^† 1	1/236 (0.42%)	0/111 (0.00%)
Respiratory tract infection ^† 1	5/236 (2.12%)	1/111 (0.90%)
Sepsis ^† 1	6/236 (2.54%)	4/111 (3.60%)
Septic shock ^† 1	3/236 (1.27%)	1/111 (0.90%)
Sinusitis ^† 1	0/236 (0.00%)	1/111 (0.90%)
Skin infection ^† 1	0/236 (0.00%)	1/111 (0.90%)
Systemic infection ^† 1	1/236 (0.42%)	0/111 (0.00%)
Tracheitis ^† 1	1/236 (0.42%)	1/111 (0.90%)
Upper respiratory tract infection ^† 1	0/236 (0.00%)	1/111 (0.90%)
Urinary tract infection ^† 1	4/236 (1.69%)	0/111 (0.00%)
Vascular device infection ^† 1	0/236 (0.00%)	1/111 (0.90%)
Wound infection ^† 1	3/236 (1.27%)	2/111 (1.80%)
Injury, poisoning and procedural complications
Humerus fracture ^† 1	0/236 (0.00%)	1/111 (0.90%)
Infusion related reaction ^† 1	3/236 (1.27%)	1/111 (0.90%)
Post procedural haemorrhage ^† 1	2/236 (0.85%)	1/111 (0.90%)
Procedural haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Shunt thrombosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Tracheostomy malfunction ^† 1	1/236 (0.42%)	0/111 (0.00%)
Vascular pseudoaneurysm ruptured ^† 1	1/236 (0.42%)	0/111 (0.00%)
Wound ^† 1	0/236 (0.00%)	1/111 (0.90%)
Wound haemorrhage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Investigations
Blood alkaline phosphatase increased ^† 1	1/236 (0.42%)	0/111 (0.00%)
Blood bilirubin increased ^† 1	1/236 (0.42%)	0/111 (0.00%)
General physical condition abnormal ^† 1	0/236 (0.00%)	1/111 (0.90%)
Liver function test abnormal ^† 1	1/236 (0.42%)	0/111 (0.00%)
Liver function test increased ^† 1	1/236 (0.42%)	0/111 (0.00%)
Platelet count decreased ^† 1	0/236 (0.00%)	1/111 (0.90%)
Transaminases increased ^† 1	1/236 (0.42%)	0/111 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	4/236 (1.69%)	1/111 (0.90%)
Dehydration ^† 1	4/236 (1.69%)	1/111 (0.90%)
Electrolyte imbalance ^† 1	0/236 (0.00%)	1/111 (0.90%)
Failure to thrive ^† 1	1/236 (0.42%)	1/111 (0.90%)
Hyperamylasaemia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hypercalcaemia ^† 1	3/236 (1.27%)	1/111 (0.90%)
Hyperglycaemia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hypernatraemia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Hyponatraemia ^† 1	4/236 (1.69%)	1/111 (0.90%)
Hypophagia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hypophosphataemia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Malnutrition ^† 1	3/236 (1.27%)	0/111 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/236 (0.42%)	0/111 (0.00%)
Fistula ^† 1	1/236 (0.42%)	0/111 (0.00%)
Musculoskeletal chest pain ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pain in extremity ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pathological fracture ^† 1	1/236 (0.42%)	0/111 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia ^† 1	1/236 (0.42%)	0/111 (0.00%)
Cancer pain ^† 1	1/236 (0.42%)	0/111 (0.00%)
Head and neck cancer ^† 1	1/236 (0.42%)	0/111 (0.00%)
Malignant neoplasm progression ^† 1	94/236 (39.83%)	55/111 (49.55%)
Malignant pleural effusion ^† 1	1/236 (0.42%)	0/111 (0.00%)
Metastases to central nervous system ^† 1	1/236 (0.42%)	0/111 (0.00%)
Neoplasm malignant ^† 1	1/236 (0.42%)	0/111 (0.00%)
Tumour haemorrhage ^† 1	2/236 (0.85%)	3/111 (2.70%)
Tumour pain ^† 1	1/236 (0.42%)	4/111 (3.60%)
Nervous system disorders
Cerebral ischaemia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Cerebrovascular accident ^† 1	1/236 (0.42%)	1/111 (0.90%)
Dizziness ^† 1	0/236 (0.00%)	2/111 (1.80%)
Encephalopathy ^† 1	1/236 (0.42%)	0/111 (0.00%)
Focal dyscognitive seizures ^† 1	1/236 (0.42%)	0/111 (0.00%)
Headache ^† 1	0/236 (0.00%)	1/111 (0.90%)
Hydrocephalus ^† 1	1/236 (0.42%)	0/111 (0.00%)
Ischaemic stroke ^† 1	1/236 (0.42%)	0/111 (0.00%)
Neuralgia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Radiculopathy ^† 1	0/236 (0.00%)	1/111 (0.90%)
Speech disorder ^† 1	1/236 (0.42%)	0/111 (0.00%)
Syncope ^† 1	1/236 (0.42%)	1/111 (0.90%)
Product Issues
Device leakage ^† 1	1/236 (0.42%)	0/111 (0.00%)
Device occlusion ^† 1	0/236 (0.00%)	1/111 (0.90%)
Psychiatric disorders
Agoraphobia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Anxiety ^† 1	1/236 (0.42%)	0/111 (0.00%)
Confusional state ^† 1	1/236 (0.42%)	0/111 (0.00%)
Delirium ^† 1	1/236 (0.42%)	0/111 (0.00%)
Suicide attempt ^† 1	0/236 (0.00%)	1/111 (0.90%)
Renal and urinary disorders
Acute kidney injury ^† 1	0/236 (0.00%)	1/111 (0.90%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	2/236 (0.85%)	1/111 (0.90%)
Bronchopneumopathy ^† 1	0/236 (0.00%)	1/111 (0.90%)
Cough ^† 1	1/236 (0.42%)	0/111 (0.00%)
Dyspnoea ^† 1	11/236 (4.66%)	2/111 (1.80%)
Emphysema ^† 1	0/236 (0.00%)	1/111 (0.90%)
Haemoptysis ^† 1	3/236 (1.27%)	2/111 (1.80%)
Hypoxia ^† 1	0/236 (0.00%)	1/111 (0.90%)
Interstitial lung disease ^† 1	1/236 (0.42%)	0/111 (0.00%)
Laryngeal oedema ^† 1	1/236 (0.42%)	1/111 (0.90%)
Laryngeal stenosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Obstructive airways disorder ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pharyngeal oedema ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pleural effusion ^† 1	2/236 (0.85%)	3/111 (2.70%)
Pneumonia aspiration ^† 1	10/236 (4.24%)	4/111 (3.60%)
Pneumonitis ^† 1	2/236 (0.85%)	0/111 (0.00%)
Pneumothorax ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pneumothorax spontaneous ^† 1	1/236 (0.42%)	0/111 (0.00%)
Pulmonary embolism ^† 1	1/236 (0.42%)	0/111 (0.00%)
Respiratory distress ^† 1	1/236 (0.42%)	3/111 (2.70%)
Respiratory failure ^† 1	5/236 (2.12%)	1/111 (0.90%)
Stridor ^† 1	2/236 (0.85%)	0/111 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema ^† 1	0/236 (0.00%)	1/111 (0.90%)
Dermatomyositis ^† 1	0/236 (0.00%)	1/111 (0.90%)
Skin mass ^† 1	1/236 (0.42%)	0/111 (0.00%)
Skin toxicity ^† 1	0/236 (0.00%)	1/111 (0.90%)
Skin ulcer ^† 1	1/236 (0.42%)	0/111 (0.00%)
Vascular disorders
Deep vein thrombosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
Haematoma ^† 1	0/236 (0.00%)	1/111 (0.90%)
Haemorrhage ^† 1	2/236 (0.85%)	0/111 (0.00%)
Hypertensive urgency ^† 1	1/236 (0.42%)	0/111 (0.00%)
Hypotension ^† 1	0/236 (0.00%)	1/111 (0.90%)
Hypovolaemic shock ^† 1	0/236 (0.00%)	1/111 (0.90%)
Shock haemorrhagic ^† 1	1/236 (0.42%)	0/111 (0.00%)
Superior vena cava syndrome ^† 1	1/236 (0.42%)	0/111 (0.00%)
Venous thrombosis ^† 1	1/236 (0.42%)	0/111 (0.00%)
1 Term from vocabulary, 24.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab 3mg/kg	Investigator Choice
	Affected / at Risk (%)	Affected / at Risk (%)
Total	210/236 (88.98%)	108/111 (97.30%)
Blood and lymphatic system disorders
Anaemia ^† 1	53/236 (22.46%)	42/111 (37.84%)
Neutropenia ^† 1	2/236 (0.85%)	9/111 (8.11%)
Thrombocytopenia ^† 1	4/236 (1.69%)	6/111 (5.41%)
Cardiac disorders
Tachycardia ^† 1	7/236 (2.97%)	7/111 (6.31%)
Endocrine disorders
Hypothyroidism ^† 1	21/236 (8.90%)	7/111 (6.31%)
Eye disorders
Lacrimation increased ^† 1	1/236 (0.42%)	6/111 (5.41%)
Gastrointestinal disorders
Constipation ^† 1	43/236 (18.22%)	21/111 (18.92%)
Diarrhoea ^† 1	47/236 (19.92%)	27/111 (24.32%)
Dry mouth ^† 1	8/236 (3.39%)	8/111 (7.21%)
Dyspepsia ^† 1	7/236 (2.97%)	6/111 (5.41%)
Dysphagia ^† 1	30/236 (12.71%)	17/111 (15.32%)
Gastrooesophageal reflux disease ^† 1	3/236 (1.27%)	8/111 (7.21%)
Nausea ^† 1	55/236 (23.31%)	37/111 (33.33%)
Stomatitis ^† 1	14/236 (5.93%)	12/111 (10.81%)
Vomiting ^† 1	28/236 (11.86%)	16/111 (14.41%)
General disorders
Asthenia ^† 1	27/236 (11.44%)	24/111 (21.62%)
Face oedema ^† 1	11/236 (4.66%)	8/111 (7.21%)
Fatigue ^† 1	67/236 (28.39%)	37/111 (33.33%)
Mucosal inflammation ^† 1	11/236 (4.66%)	19/111 (17.12%)
Oedema peripheral ^† 1	19/236 (8.05%)	5/111 (4.50%)
Pyrexia ^† 1	37/236 (15.68%)	16/111 (14.41%)
Infections and infestations
Oral candidiasis ^† 1	11/236 (4.66%)	6/111 (5.41%)
Pneumonia ^† 1	16/236 (6.78%)	5/111 (4.50%)
Respiratory tract infection ^† 1	6/236 (2.54%)	6/111 (5.41%)
Investigations
Alanine aminotransferase increased ^† 1	9/236 (3.81%)	6/111 (5.41%)
Aspartate aminotransferase increased ^† 1	14/236 (5.93%)	6/111 (5.41%)
Blood alkaline phosphatase increased ^† 1	18/236 (7.63%)	3/111 (2.70%)
Lipase increased ^† 1	13/236 (5.51%)	2/111 (1.80%)
Lymphocyte count decreased ^† 1	8/236 (3.39%)	6/111 (5.41%)
Weight decreased ^† 1	35/236 (14.83%)	19/111 (17.12%)
White blood cell count decreased ^† 1	3/236 (1.27%)	8/111 (7.21%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	46/236 (19.49%)	21/111 (18.92%)
Hypercalcaemia ^† 1	17/236 (7.20%)	8/111 (7.21%)
Hyperglycaemia ^† 1	16/236 (6.78%)	9/111 (8.11%)
Hypoalbuminaemia ^† 1	12/236 (5.08%)	4/111 (3.60%)
Hypokalaemia ^† 1	11/236 (4.66%)	7/111 (6.31%)
Hyponatraemia ^† 1	25/236 (10.59%)	15/111 (13.51%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	19/236 (8.05%)	2/111 (1.80%)
Back pain ^† 1	17/236 (7.20%)	0/111 (0.00%)
Neck pain ^† 1	17/236 (7.20%)	9/111 (8.11%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain ^† 1	13/236 (5.51%)	8/111 (7.21%)
Nervous system disorders
Dizziness ^† 1	9/236 (3.81%)	7/111 (6.31%)
Headache ^† 1	23/236 (9.75%)	4/111 (3.60%)
Neuropathy peripheral ^† 1	6/236 (2.54%)	9/111 (8.11%)
Paraesthesia ^† 1	4/236 (1.69%)	6/111 (5.41%)
Psychiatric disorders
Anxiety ^† 1	9/236 (3.81%)	9/111 (8.11%)
Depression ^† 1	12/236 (5.08%)	3/111 (2.70%)
Insomnia ^† 1	13/236 (5.51%)	7/111 (6.31%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	37/236 (15.68%)	13/111 (11.71%)
Dyspnoea ^† 1	32/236 (13.56%)	12/111 (10.81%)
Epistaxis ^† 1	5/236 (2.12%)	11/111 (9.91%)
Pleural effusion ^† 1	5/236 (2.12%)	6/111 (5.41%)
Productive cough ^† 1	14/236 (5.93%)	2/111 (1.80%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	4/236 (1.69%)	16/111 (14.41%)
Dry skin ^† 1	14/236 (5.93%)	12/111 (10.81%)
Erythema ^† 1	3/236 (1.27%)	6/111 (5.41%)
Pruritus ^† 1	23/236 (9.75%)	1/111 (0.90%)
Rash ^† 1	22/236 (9.32%)	6/111 (5.41%)
Vascular disorders
Hypertension ^† 1	16/236 (6.78%)	4/111 (3.60%)
1 Term from vocabulary, 24.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Bristol-Myers Squibb Study Director
Organization:	Bristol-Myers Squibb
EMail:	Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Saba NF, Blumenschein G Jr, Guigay J, Licitra L, Fayette J, Harrington KJ, Kiyota N, Gillison ML, Ferris RL, Jayaprakash V, Li L, Brossart P. Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age. Oral Oncol. 2019 Sep;96:7-14. doi: 10.1016/j.oraloncology.2019.06.017. Epub 2019 Jul 3.

Cocks K, Contente M, Simpson S, DeRosa M, Taylor FC, Shaw JW. A Q-TWiST Analysis Comparing Nivolumab and Therapy of Investigator's Choice in Patients with Recurrent/Metastatic Platinum-Refractory Squamous Cell Carcinoma of the Head and Neck. Pharmacoeconomics. 2019 Aug;37(8):1041-1047. doi: 10.1007/s40273-019-00798-1.

Pai SI, Faivre S, Licitra L, Machiels JP, Vermorken JB, Bruzzi P, Gruenwald V, Giglio RE, Leemans CR, Seiwert TY, Soulieres D. Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). J Immunother Cancer. 2019 Apr 3;7(1):96. doi: 10.1186/s40425-019-0578-0.

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Lynch M, Jayaprakash V, Li L, Gillison ML. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018 Jun;81:45-51. doi: 10.1016/j.oraloncology.2018.04.008. Epub 2018 Apr 17.

Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen CJ, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Sum Kenneth Li W, Ferris RL, Gillison M, Namba Y, Monga M, Lynch M, Tahara M. A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol. 2017 Oct;73:138-146. doi: 10.1016/j.oraloncology.2017.07.023. Epub 2017 Sep 1.

Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, Kasper S, Even C, Vokes EE, Worden F, Saba NF, Kiyota N, Haddad R, Tahara M, Grunwald V, Shaw JW, Monga M, Lynch M, Taylor F, DeRosa M, Morrissey L, Cocks K, Gillison ML, Guigay J. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1104-1115. doi: 10.1016/S1470-2045(17)30421-7. Epub 2017 Jun 23.

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.

Layout table for additonal information

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02105636
Other Study ID Numbers:	CA209-141 2013-003622-86 ( EudraCT Number )
First Submitted:	April 3, 2014
First Posted:	April 7, 2014
Results First Submitted:	November 15, 2016
Results First Posted:	January 11, 2017
Last Update Posted:	October 5, 2022

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