History of Changes for Study: NCT02105636

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

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Study Record Versions

Version	Submitted Date	Changes
1	April 4, 2014	None (earliest Version on record)
2	May 5, 2014	Recruitment Status, Study Status, Contacts/Locations and References
3	May 7, 2014	Study Status and Contacts/Locations
4	May 27, 2014	Study Status and Contacts/Locations
5	May 30, 2014	Study Status
6	June 12, 2014	Contacts/Locations and Study Status
7	June 25, 2014	Contacts/Locations and Study Status
8	July 9, 2014	Contacts/Locations and Study Status
9	July 23, 2014	Contacts/Locations and Study Status
10	August 11, 2014	Contacts/Locations and Study Status
11	August 28, 2014	Contacts/Locations and Study Status
12	September 22, 2014	Contacts/Locations and Study Status
13	November 3, 2014	Contacts/Locations and Study Status
14	November 10, 2014	Contacts/Locations, Sponsor/Collaborators and Study Status
15	November 20, 2014	Contacts/Locations and Study Status
16	November 26, 2014	Contacts/Locations and Study Status
17	December 5, 2014	Contacts/Locations and Study Status
18	December 10, 2014	Study Status and Contacts/Locations
19	December 31, 2014	Study Status
20	January 27, 2015	Contacts/Locations and Study Status
21	February 6, 2015	Contacts/Locations and Study Status
22	February 19, 2015	Study Status
23	March 5, 2015	Contacts/Locations and Study Status
24	March 18, 2015	Outcome Measures, Contacts/Locations, Study Status, Eligibility, Study Design and Study Description
25	April 10, 2015	Contacts/Locations and Study Status
26	April 20, 2015	Contacts/Locations and Study Status
27	May 6, 2015	Contacts/Locations and Study Status
28	May 20, 2015	Contacts/Locations and Study Status
29	June 3, 2015	Study Status
30	June 22, 2015	Contacts/Locations and Study Status
31	July 3, 2015	Contacts/Locations and Study Status
32	July 17, 2015	Contacts/Locations and Study Status
33	August 6, 2015	Contacts/Locations and Study Status
34	August 19, 2015	Contacts/Locations and Study Status
35	September 2, 2015	Contacts/Locations and Study Status
36	September 16, 2015	Contacts/Locations and Study Status
37	October 5, 2015	Contacts/Locations and Study Status
38	October 15, 2015	Study Status
39	November 4, 2015	Contacts/Locations and Study Status
40	November 18, 2015	Contacts/Locations and Study Status
41	December 8, 2015	Study Status
42	December 21, 2015	Study Status
43	January 12, 2016	Recruitment Status, Contacts/Locations and Study Status
44	January 21, 2016	Contacts/Locations and Study Status
45	January 26, 2016	Study Status
46	February 10, 2016	Study Status
47	February 25, 2016	Study Status
48	March 11, 2016	Study Status
49	March 28, 2016	Study Status
50	April 12, 2016	Study Status
51	April 25, 2016	Study Status
52	May 10, 2016	Study Status
53	May 25, 2016	Study Status
54	June 9, 2016	Study Status
55	July 11, 2016	Study Status
56	July 26, 2016	Study Status
57	July 28, 2016	Study Status
58	August 8, 2016	Study Status
59	August 23, 2016	Study Status
60	November 15, 2016	Outcome Measures, Study Status, More Information, Study Design, Adverse Events, Baseline Characteristics and Participant Flow
61	January 10, 2017	Study Status and Baseline Characteristics
62	October 3, 2017	Study Status, References, Outcome Measures, Baseline Characteristics and Contacts/Locations
63	July 16, 2018	Contacts/Locations, Study Status and References
64	June 13, 2019	References, Study Status and Contacts/Locations
65	September 27, 2019	Study Status and Outcome Measures
66	December 14, 2021	Recruitment Status, Contacts/Locations, Study Status, Oversight, Outcome Measures and References
67	September 6, 2022	Outcome Measures, Adverse Events, Participant Flow, Baseline Characteristics, Contacts/Locations, Study Status and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CA209-141
Brief Title:	Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)
Official Title:	An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Secondary IDs:	2013-003622-86 [EudraCT Number]

Study Status


Record Verification:	December 2021
Overall Status:	Completed
Study Start:	May 29, 2014
Primary Completion:	November 6, 2015 [Actual]
Study Completion:	September 10, 2021 [Actual]

First Submitted:	April 3, 2014
First Submitted that Met QC Criteria:	April 4, 2014
First Posted:	April 7, 2014 [Estimate]

Results First Submitted:	November 15, 2016
Results First Submitted that Met QC Criteria:	November 15, 2016
Results First Posted:	January 11, 2017 [Estimate]

Certification/Extension First Submitted:	July 28, 2016
Certification/Extension First Submitted that Met QC Criteria:	July 28, 2016
Certification/Extension First Posted:	August 1, 2016 [Estimate]

Last Update Submitted that Met QC Criteria:	December 14, 2021
Last Update Posted:	January 4, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Bristol-Myers Squibb
Responsible Party:	Sponsor
Collaborators:	Ono Pharmaceutical Co. Ltd

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


Brief Summary:	The purpose of this study is to find out whether Nivolumab will significantly improve overall survival as compared to therapy of investigator's choice in patients with recurrent or metastatic head and neck carcinoma.
Detailed Description:

Conditions


Conditions:	Squamous Cell Carcinoma of the Head and Neck
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	506 [Actual]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Arm A: Nivolumab Nivolumab 3mg/kg intravenous (IV) Solution for Injection every 2 weeks until disease progression	Drug: Nivolumab Other Names: BMS-936558
Active Comparator: Arm B: Cetuximab/Methotrexate/Docetaxel 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: CetuximabDrug: MethotrexateDrug: Docetaxel

Outcome Measures

[See Results Section.]


Primary Outcome Measures:
1.	Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: From date of randomization to date of death, approximately 18 months ] Overall survival 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. 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. Interim analysis (Primary Endpoint) occurred at 218 deaths.
2.	Overall Survival (OS) Rate in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization to 3, 6, 9, and 12 months ] The overall survival rate is the probability that a participant will be alive at 3, 6, 9, and 12 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Secondary Outcome Measures:
1.	Progression-Free Survival (PFS) [ Time Frame: Randomization to disease progression or death, whichever occurs first; Approximately 5 years ] 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 (RECIST) 1.1 criteria), or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants without any on study tumor assessments and did not die were censored on their date of randomization. Participants who 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.
2.	Objective Response Rate (ORR) [ Time Frame: Randomization to disease progression or study drug is discontinued, whichever occurs first; Approximately 5 years ] ORR was defined as the proportion 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. Best overall response (BOR) was defined as the best response designation, recorded between the date of randomization and the date of progression, as assessed by the investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response assessments will contribute to the BOR assessment. For participants who continue treatment beyond progression, the BOR was determined based on response assessments up to the time of initial RECIST 1.1 progression.
Other Outcome Measures:
1.	Number of Participants With Death, Study Drug-Related Death, Serious Adverse Events (SAEs), and Study Drug-Related SAEs in All Treated Participants at Primary Endpoint [ Time Frame: Date of first dose of study drug to 30 days post last dose of study drug, approximately 18 months ] AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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

Contacts/Locations


Study Officials:	Bristol-Myers Squibb Study Director Bristol-Myers Squibb
Locations:	United States, California
	Stanford University Medical Center Stanford, California, United States, 94305
	United States, Florida
	H. Lee Moffitt Cancer Center Tampa, Florida, United States, 33612
	United States, Georgia
	Winship Cancer Institute Atlanta, Georgia, United States, 30322
	United States, Illinois
	University Of Chicago Chicago, Illinois, United States, 60637
	United States, Louisiana
	Crescent City Research Consortium, LLC Metairie, Louisiana, United States, 70006
	United States, Massachusetts
	Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
	Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
	United States, Michigan
	University Of Michigan Ann Arbor, Michigan, United States, 48109
	United States, North Carolina
	Dumc Durham, North Carolina, United States, 27710
	United States, Ohio
	Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210
	United States, Pennsylvania
	UPMC Cancer Center Pittsburgh, Pennsylvania, United States, 15213
	United States, Tennessee
	Vanderbilt Cancer Clinic Nashville, Tennessee, United States, 37232
	United States, Texas
	Univ Of Tx. Md Anderson Hoston, Texas, United States, 77030
	United States, Utah
	Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112
	United States, Wisconsin
	Medical College of Wisconsin Milwaukee, Wisconsin, United States, 53226
	Argentina
	Instituto Oncologico De Cordoba Cordoba, Argentina, 5000
	Argentina, Buenos Aires
	COIBA Berazategui, Buenos Aires, Argentina, 1880
	Argentina, Tucuman
	Centro Para La Atencion Integral Del Paciente Oncologico San Miguel De Tucuman, Tucuman, Argentina, 4000
	Brazil
	Local Institution Sao Paulo, Brazil, 01321-001
	Brazil, Rio Grande Do Sul
	Local Institution Ijui, Rio Grande Do Sul, Brazil, 98700-000
	Local Institution Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
	Canada, British Columbia
	BC Cancer - Vancouver Vancouver, British Columbia, Canada, V5Z 4E6
	Canada, Ontario
	London Regional Cancer Program London, Ontario, Canada, N6A 4L6
	France
	Local Institution Lyon Cedex 08, France, 69373
	Local Institution Nice Cedex 2, France, 06189
	Local Institution Villejuif Cedex, France, 94805
	Germany
	Local Institution Berlin, Germany, 12200
	Universitaetsklinikum Bonn Bonn, Germany, 53127
	Universitaetsklinikum Essen Essen, Germany, 45122
	Uniklinikum Hamburg-Eppendorf Hamburg, Germany, 20246
	Med Hochschule Hannover Hannover, Germany, 30625
	Klinikum Der Universitaet Wuerzburg, Germany, 97070
	Hong Kong
	Local Institution Hong Kong, Hong Kong
	Italy
	Local Institution Milano, Italy, 20142
	Local Institution Napoli, Italy, 80131
	Local Institution Padova, Italy, 35128
	Italy, FC
	Ist.Scient. Romagnolo Per Lo Studio E Cura Tumori Meldola, FC, Italy, 47014
	Italy, MI
	Local Institution Milano, MI, Italy, 20133
	Italy, TO
	Local Institution Torino, TO, Italy, 10126
	Japan
	Local Institution Akashi, Hyogo, Japan, 673-8558
	Local Institution Tokyo, Japan, 135-8550
	Japan, Aichi
	Local Institution Nagoya, Aichi, Japan, 4648681
	Japan, Chiba
	Local Institution Kashiwa, Chiba, Japan, 2778577
	Japan, Hokkaido
	Local Institution Sapporo-shi, Hokkaido, Japan, 0608648
	Japan, Hyogo
	Local Institution Kobe-shi, Hyogo, Japan, 650-0017
	Japan, Osaka
	Local Institution Takatsuki, Osaka, Japan, 5698686
	Japan, Shizuoka
	Local Institution Sunto-gun, Shizuoka, Japan, 4118777
	Korea, Republic of
	Local Institution Seoul, Korea, Republic of, 135-710
	Local Institution Seoul, Korea, Republic of, 137-701
	Netherlands
	Local Institution Amsterdam, Netherlands, 1081 HV
	Local Institution Groningen, Netherlands, 9713 AP
	Local Institution Leiden, Netherlands, 2333 ZA
	Spain
	Local Institution Barcelona, Spain, 08035
	Local Institution Barcelona, Spain, 08036
	Local Institution Madrid, Spain, 28041
	Local Institution Valencia, Spain, 46010
	Switzerland
	Universitatsspital Zurich Zuerich, Switzerland, 8091
	Taiwan
	Local Institution Tainan, Taiwan, 704
	Local Institution Taipei, Taiwan, 100
	United Kingdom
	Local Institution Surrey, United Kingdom, SM2 5PT
	United Kingdom, Greater London
	Local Institution London, Greater London, United Kingdom, SW3 6JJ
	United Kingdom, Greater Manchester
	Local Institution Manchester, Greater Manchester, United Kingdom, M20 4BX
	United Kingdom, Hampshire
	Local Institution Southampton, Hampshire, United Kingdom, SO16 6YD
	United Kingdom, Merseyside
	Local Institution Wirral, Merseyside, United Kingdom, CH63 4JY

IPDSharing


Plan to Share IPD:

References


Links:	URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html Description: BMS Clinical Trial Information
	URL: https://www.bmsstudyconnect.com/s/US/English/USenHome Description: BMS Clinical Trial Patient Recruiting
	URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html Description: Investigator Inquiry Form
	URL: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm Description: FDA Safety Alerts and Recalls
Available IPD/Information:

Participant Flow

Recruitment Details

506 enrolled, 361 randomized. Non-randomized reasons: 5 adverse events, 18 withdrew consent, 7 died, 108 no longer met study criteria, 7 other. 347 treated (236 nivo, 111 IC). Non-treatment reasons: 1 disease progression, 3 request to discontinue treatment, 6 withdrew consent, 4 no longer met study criteria. Nivo=nivolumab, IC=investigator's choice

Pre-assignment Details

Arm/Group Title

Nivolumab 3mg/kg

Cetuximab/Methotrexate/Docetaxel

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 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 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: Overall Study

Started

236

111

Completed

41^[1]

3^[1]

Not Completed

195

108

Reason Not Completed

Disease Progression

162

Study Drug Toxicity

Adverse Event Unrelated to Study Drug

Subject Request to Discontinue Treatment

Subject Withdrew Consent

Maximum Clinical Benefit

Poor/Non-compliance

Reason Not Specified

Not Reported

[1]	Completed=Still on Treatment

Baseline Characteristics

Arm/Group Title

Nivolumab 3mg/kg

Cetuximab/Methotrexate/Docetaxel

Total

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.

Total of all reporting groups

Overall Number of Baseline Participants

240

121

361

Baseline Analysis Population Description

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

248

>=65 and <75 years

>=75 years

Sex: Female, Male

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

240 Participants

121 Participants

361 Participants

Female

17.92%

14.88%

16.9%

Male

197

82.08%

103

85.12%

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

Asian

Other

Race/Ethnicity, Customized

Measure Type: Number
Unit of measure: participants

Number Analyzed

240 Participants

121 Participants

361 Participants

Hispanic/Latino

Not Hispanic/Latino

132

192

Not Reported

156

Eastern Cooperative Oncology Group (ECOG) Performance Status^[1]

Measure Type: Number
Unit of measure: participants

Number Analyzed

240 Participants

121 Participants

361 Participants

189

283

>=2

Not Reported

[1]

Measure Description: ECOG is a 6-item scale used to assess disease progression, daily functioning, appropriate treatment, and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all pre-disease performance without restriction and (worst score) 5=death.

Outcome Measures

1. Primary Outcome:

Title

Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint

Description

Overall survival 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. 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. Interim analysis (Primary Endpoint) occurred at 218 deaths.

Time Frame

From date of randomization to date of death, approximately 18 months

Outcome Measure Data

Analysis Population Description

All randomized participants.


Arm/Group Title	Nivolumab 3mg/kg	Cetuximab/Methotrexate/Docetaxel
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 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 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, Cetuximab/Methotrexate/Docetaxel
	Comments	Stratified Cox proportional hazard model. HR = Nivolumab over investigator's choice therapy (Cetuximab, Methotrexate, or Docetaxel)
	Type of Statistical Test	Superiority or Other (legacy)
	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	[Not specified]

2. Primary Outcome:

Title

Overall Survival (OS) Rate in All Randomized Participants at Primary Endpoint

Description

The overall survival rate is the probability that a participant will be alive at 3, 6, 9, and 12 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.

Time Frame

Randomization to 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3mg/kg	Cetuximab/Methotrexate/Docetaxel
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 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 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
Number (95% Confidence Interval) Unit of Measure: percent probability of OS
3 months	71.5(65.3 to 76.8)	74.0(65.1 to 81.0)
6 months	55.6(48.9 to 61.8)	41.8(32.6 to 50.7)
9 months	43.4(36.2 to 50.3)	29.1(20.3 to 38.5)
12 months	36.0(28.5 to 43.4)	16.6(8.6 to 26.8)

3. Secondary Outcome:


Title	Progression-Free Survival (PFS)
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 (RECIST) 1.1 criteria), or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants without any on study tumor assessments and did not die were censored on their date of randomization. Participants who 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	Randomization to disease progression or death, whichever occurs first; Approximately 5 years
Anticipated Reporting Date	September 2022
Outcome Measure Data Not Reported

4. Secondary Outcome:


Title	Objective Response Rate (ORR)
Description	ORR was defined as the proportion 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. Best overall response (BOR) was defined as the best response designation, recorded between the date of randomization and the date of progression, as assessed by the investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response assessments will contribute to the BOR assessment. For participants who continue treatment beyond progression, the BOR was determined based on response assessments up to the time of initial RECIST 1.1 progression.
Time Frame	Randomization to disease progression or study drug is discontinued, whichever occurs first; Approximately 5 years
Anticipated Reporting Date	September 2022
Outcome Measure Data Not Reported

5. Other Pre-specified Outcome:

Title

Number of Participants With Death, Study Drug-Related Death, Serious Adverse Events (SAEs), and Study Drug-Related SAEs in All Treated Participants at Primary Endpoint

Description

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Time Frame

Date of first dose of study drug to 30 days post last dose of study drug, approximately 18 months

Outcome Measure Data

Analysis Population Description

All Treated Participants: All randomized participants who received at least one dose of study drug


Arm/Group Title	Nivolumab 3mg/kg	Cetuximab/Methotrexate/Docetaxel
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 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigator's Choice.
Overall Number of Participants Analyzed	236	111
Measure Type: Number Unit of Measure: participants
Deaths	50 21.2%	21 18.9%
Study Drug-Related Deaths	2 0.8%	0 0%
SAEs	127 53.8%	66 59.5%
Study Drug-Related SAEs	16 6.8%	17 15.3%
AEs Leading to Discontinuation	51 21.6%	27 24.3%
Study Drug-Related AEs Leading to Discontinuation	9 3.8%	11 9.9%

Adverse Events


Time Frame	From first dose to last dose plus 30 days up to Primary Endpoint, approximately 18 months (November 2015)
Adverse Event Reporting Description	Study initiated: May 2014; Primary Endpoint: November 2015 (study on-going)

Arm/Group Title	Nivolumab 3 mg/kg	Cetuximab/Methotrexate/Docetaxel
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 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 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 3 mg/kg	Cetuximab/Methotrexate/Docetaxel
	Affected / At Risk (%)	Affected / At Risk (%)
Total	/	/
Serious Adverse Events
	Nivolumab 3 mg/kg	Cetuximab/Methotrexate/Docetaxel
	Affected / At Risk (%)	Affected / At Risk (%)
Total	127 / 236 (53.81%)	66 / 111 (59.46%)
Blood and lymphatic system disorders
Anaemia ^{† A}	0 / 236 (0%)	2 / 111 (1.8%)
Leukopenia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Cardiac disorders
Acute myocardial infarction ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Atrial fibrillation ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Atrial flutter ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Cardiac arrest ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Cardiac failure ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Cardio-respiratory arrest ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Cardiopulmonary failure ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Cardiovascular disorder ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Pericarditis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Supraventricular tachycardia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Ear and labyrinth disorders
Vertigo ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Endocrine disorders
Hypophysitis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Secondary adrenocortical insufficiency ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Secondary hypothyroidism ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Eye disorders
Blindness unilateral ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Visual acuity reduced ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Gastrointestinal disorders
Abdominal pain ^{† A}	1 / 236 (0.42%)	2 / 111 (1.8%)
Colitis ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Diarrhoea ^{† A}	0 / 236 (0%)	2 / 111 (1.8%)
Dysphagia ^{† A}	2 / 236 (0.85%)	3 / 111 (2.7%)
Gastric disorder ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Gastric haemorrhage ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Gastritis ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Nausea ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Oesophageal stenosis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Parotid gland haemorrhage ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pneumoperitoneum ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Stomatitis ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Tongue haemorrhage ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
General disorders
Asthenia ^{† A}	1 / 236 (0.42%)	2 / 111 (1.8%)
Catheter site pain ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Chills ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Device occlusion ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Disease progression ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Drug intolerance ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Face oedema ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Fatigue ^{† A}	2 / 236 (0.85%)	1 / 111 (0.9%)
General physical health deterioration ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Localised oedema ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Malaise ^{† A}	0 / 236 (0%)	2 / 111 (1.8%)
Mucosal inflammation ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Pain ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Pyrexia ^{† A}	3 / 236 (1.27%)	4 / 111 (3.6%)
Ulcer haemorrhage ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Immune system disorders
Allergic granulomatous angiitis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Infections and infestations
Cellulitis ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Clostridium difficile colitis ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Device related infection ^{† A}	0 / 236 (0%)	2 / 111 (1.8%)
Gastrointestinal infection ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Infection ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Localised infection ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Lower respiratory tract infection ^{† A}	3 / 236 (1.27%)	3 / 111 (2.7%)
Lung infection ^{† A}	4 / 236 (1.69%)	4 / 111 (3.6%)
Lymphangitis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Neutropenic sepsis ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Otitis media ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Peritonitis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pneumonia ^{† A}	10 / 236 (4.24%)	1 / 111 (0.9%)
Pneumonia bacterial ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Purulent discharge ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Respiratory tract infection ^{† A}	5 / 236 (2.12%)	1 / 111 (0.9%)
Sepsis ^{† A}	5 / 236 (2.12%)	3 / 111 (2.7%)
Skin infection ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Tracheitis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Upper respiratory tract infection ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Urinary tract infection ^{† A}	4 / 236 (1.69%)	0 / 111 (0%)
Wound infection ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Injury, poisoning and procedural complications
Infusion related reaction ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Post procedural haemorrhage ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Tracheostomy malfunction ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Vascular pseudoaneurysm ruptured ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Wound haemorrhage ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Investigations
Blood alkaline phosphatase increased ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Blood bilirubin increased ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Liver function test abnormal ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Platelet count decreased ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Transaminases increased ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Metabolism and nutrition disorders
Decreased appetite ^{† A}	4 / 236 (1.69%)	1 / 111 (0.9%)
Dehydration ^{† A}	3 / 236 (1.27%)	0 / 111 (0%)
Hypercalcaemia ^{† A}	3 / 236 (1.27%)	1 / 111 (0.9%)
Hyperglycaemia ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Hypernatraemia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Hyponatraemia ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Hypophagia ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Hypophosphataemia ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Malnutrition ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Musculoskeletal and connective tissue disorders
Back pain ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Bone pain ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Musculoskeletal chest pain ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pain in extremity ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Head and neck cancer ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Malignant neoplasm progression ^{† A}	43 / 236 (18.22%)	25 / 111 (22.52%)
Malignant pleural effusion ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Metastases to central nervous system ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Neoplasm malignant ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Tumour haemorrhage ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Tumour pain ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Nervous system disorders
Cerebrovascular accident ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Complex partial seizures ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Dizziness ^{† A}	0 / 236 (0%)	2 / 111 (1.8%)
Encephalopathy ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Headache ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Hydrocephalus ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Ischaemic stroke ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Neuralgia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Speech disorder ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Syncope ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Psychiatric disorders
Agoraphobia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Delirium ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Renal and urinary disorders
Acute kidney injury ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Bronchopneumopathy ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Dyspnoea ^{† A}	9 / 236 (3.81%)	1 / 111 (0.9%)
Haemoptysis ^{† A}	2 / 236 (0.85%)	1 / 111 (0.9%)
Hypoxia ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Laryngeal oedema ^{† A}	1 / 236 (0.42%)	1 / 111 (0.9%)
Laryngeal stenosis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Obstructive airways disorder ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pharyngeal oedema ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pleural effusion ^{† A}	2 / 236 (0.85%)	3 / 111 (2.7%)
Pneumonia aspiration ^{† A}	8 / 236 (3.39%)	2 / 111 (1.8%)
Pneumonitis ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Pneumothorax ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Pneumothorax spontaneous ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Respiratory distress ^{† A}	1 / 236 (0.42%)	2 / 111 (1.8%)
Respiratory failure ^{† A}	4 / 236 (1.69%)	0 / 111 (0%)
Stridor ^{† A}	2 / 236 (0.85%)	0 / 111 (0%)
Skin and subcutaneous tissue disorders
Angioedema ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Dermatomyositis ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Skin mass ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Skin ulcer ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Vascular disorders
Haematoma ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Haemorrhage ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Hypertensive crisis ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Hypotension ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Hypovolaemic shock ^{† A}	0 / 236 (0%)	1 / 111 (0.9%)
Shock haemorrhagic ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
Superior vena cava syndrome ^{† A}	1 / 236 (0.42%)	0 / 111 (0%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab 3 mg/kg	Cetuximab/Methotrexate/Docetaxel
	Affected / At Risk (%)	Affected / At Risk (%)
Total	202 / 236 (85.59%)	105 / 111 (94.59%)
Blood and lymphatic system disorders
Anaemia ^{† A}	44 / 236 (18.64%)	36 / 111 (32.43%)
Neutropenia ^{† A}	1 / 236 (0.42%)	9 / 111 (8.11%)
Thrombocytopenia ^{† A}	3 / 236 (1.27%)	6 / 111 (5.41%)
Cardiac disorders
Tachycardia ^{† A}	3 / 236 (1.27%)	6 / 111 (5.41%)
Endocrine disorders
Hypothyroidism ^{† A}	15 / 236 (6.36%)	6 / 111 (5.41%)
Eye disorders
Lacrimation increased ^{† A}	1 / 236 (0.42%)	6 / 111 (5.41%)
Gastrointestinal disorders
Constipation ^{† A}	36 / 236 (15.25%)	20 / 111 (18.02%)
Diarrhoea ^{† A}	35 / 236 (14.83%)	25 / 111 (22.52%)
Dry mouth ^{† A}	7 / 236 (2.97%)	6 / 111 (5.41%)
Dysphagia ^{† A}	28 / 236 (11.86%)	13 / 111 (11.71%)
Gastrooesophageal reflux disease ^{† A}	2 / 236 (0.85%)	8 / 111 (7.21%)
Nausea ^{† A}	45 / 236 (19.07%)	34 / 111 (30.63%)
Stomatitis ^{† A}	7 / 236 (2.97%)	11 / 111 (9.91%)
Vomiting ^{† A}	27 / 236 (11.44%)	14 / 111 (12.61%)
General disorders
Asthenia ^{† A}	24 / 236 (10.17%)	23 / 111 (20.72%)
Face oedema ^{† A}	10 / 236 (4.24%)	8 / 111 (7.21%)
Fatigue ^{† A}	62 / 236 (26.27%)	35 / 111 (31.53%)
Mucosal inflammation ^{† A}	8 / 236 (3.39%)	17 / 111 (15.32%)
Oedema peripheral ^{† A}	18 / 236 (7.63%)	5 / 111 (4.5%)
Pyrexia ^{† A}	29 / 236 (12.29%)	12 / 111 (10.81%)
Infections and infestations
Oral candidiasis ^{† A}	6 / 236 (2.54%)	6 / 111 (5.41%)
Respiratory tract infection ^{† A}	4 / 236 (1.69%)	6 / 111 (5.41%)
Investigations
Aspartate aminotransferase increased ^{† A}	12 / 236 (5.08%)	4 / 111 (3.6%)
Blood alkaline phosphatase increased ^{† A}	17 / 236 (7.2%)	3 / 111 (2.7%)
Weight decreased ^{† A}	31 / 236 (13.14%)	16 / 111 (14.41%)
Metabolism and nutrition disorders
Decreased appetite ^{† A}	41 / 236 (17.37%)	21 / 111 (18.92%)
Hypercalcaemia ^{† A}	15 / 236 (6.36%)	7 / 111 (6.31%)
Hyperglycaemia ^{† A}	12 / 236 (5.08%)	9 / 111 (8.11%)
Hypokalaemia ^{† A}	8 / 236 (3.39%)	8 / 111 (7.21%)
Hyponatraemia ^{† A}	21 / 236 (8.9%)	14 / 111 (12.61%)
Musculoskeletal and connective tissue disorders
Back pain ^{† A}	12 / 236 (5.08%)	0 / 111 (0%)
Neck pain ^{† A}	12 / 236 (5.08%)	8 / 111 (7.21%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain ^{† A}	13 / 236 (5.51%)	6 / 111 (5.41%)
Nervous system disorders
Headache ^{† A}	21 / 236 (8.9%)	3 / 111 (2.7%)
Neuropathy peripheral ^{† A}	4 / 236 (1.69%)	8 / 111 (7.21%)
Psychiatric disorders
Anxiety ^{† A}	8 / 236 (3.39%)	7 / 111 (6.31%)
Insomnia ^{† A}	12 / 236 (5.08%)	7 / 111 (6.31%)
Respiratory, thoracic and mediastinal disorders
Cough ^{† A}	32 / 236 (13.56%)	10 / 111 (9.01%)
Dyspnoea ^{† A}	27 / 236 (11.44%)	11 / 111 (9.91%)
Epistaxis ^{† A}	4 / 236 (1.69%)	11 / 111 (9.91%)
Pleural effusion ^{† A}	5 / 236 (2.12%)	6 / 111 (5.41%)
Productive cough ^{† A}	12 / 236 (5.08%)	2 / 111 (1.8%)
Skin and subcutaneous tissue disorders
Alopecia ^{† A}	2 / 236 (0.85%)	14 / 111 (12.61%)
Dry skin ^{† A}	11 / 236 (4.66%)	12 / 111 (10.81%)
Erythema ^{† A}	3 / 236 (1.27%)	6 / 111 (5.41%)
Pruritus ^{† A}	20 / 236 (8.47%)	0 / 111 (0%)
Rash ^{† A}	20 / 236 (8.47%)	5 / 111 (4.5%)
Vascular disorders
Hypertension ^{† A}	14 / 236 (5.93%)	3 / 111 (2.7%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA 18.1

Limitations and Caveats


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Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study. There IS an agreement between the Principal Investigator 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:
Name/Official Title:	Bristol-Myers Squibb Study Director
Organization:	Bristol-Myers Squibb
Phone:
Email:	Clinical.Trials@bms.com