Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (CheckMate 714)

A Double-Blind, Randomized, Two Arm Phase 2 Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

A study in patients with metastatic or recurrent squamous cell cancer of the head and neck to evaluate the effectiveness of Nivolumab plus Ipilumumab vs. Nivolumab alone (CheckMate 714)

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Other: Placebo; Biological: Nivolumab; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 425
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Local Institution - 0111
  • Buenos Aires
    • Pergamino, Buenos Aires, Argentina
      • Local Institution - 0121
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0023
  • Sint-Niklaas, Belgium, 9100
    • Local Institution - 0074
  • Yvoir, Belgium, 5530
    • Local Institution - 0053
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Local Institution
  • Sao Paulo, Brazil, 04039-004
    • Local Institution - 0049
  • Sao Paulo, Brazil, 05403-010
    • Local Institution - 0050
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Local Institution - 0046
    • Ipatinga, Minas Gerais, Brazil, 35160-158
      • Local Institution - 0124
  • Parana
    • Curitiba, Parana, Brazil, 81480-580
      • Local Institution - 0047
  • RIO Grande DO SUL
    • Caxias do Sul, RIO Grande DO SUL, Brazil, 95070-560
      • Local Institution - 0125
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Local Institution - 0051
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
      • Local Institution - 0052
  • SAO Paulo
    • Sao Jose do Rio Preto, SAO Paulo, Brazil, 15090-000
      • Local Institution - 0048
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Local Institution - 0045
    • Santo Andre, Sao Paulo, Brazil, 09060-870
      • Local Institution - 0123
• Canada
  • Quebec, Canada, G1J 1Z4
    • Local Institution - 0014
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0013
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0056
    • Toronto, Ontario, Canada, M5G 1Z5
      • Local Institution - 0012
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0016
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile
      • Local Institution - 0115
• Czechia
  • Brno, Czechia, 656 53
    • Local Institution - 0022
  • Hradec Kralove, Czechia, 500 05
    • Local Institution - 0020
  • Olomouc, Czechia, 779 00
    • Local Institution - 0021
• Finland
  • Helsinki, Finland, 00290
    • Local Institution - 0069
• France
  • Amiens Cedex 1, France, 80054
    • Local Institution - 0032
  • Bordeaux, France, 33075
    • Local Institution - 0120
  • Clermont Ferrand cedex 01, France, 63011
    • Local Institution - 0073
  • Clichy, France, 92110
    • Local Institution - 0089
  • Lyon Cedex 08, France, 69373
    • Local Institution - 0029
  • Marseille Cedex 5, France, 13385
    • Local Institution - 0075
  • Nice, France, 06189
    • Local Institution - 0079
  • Rennes Cedex, France, 35042
    • Local Institution - 0030
  • Villejuif, France, 94805
    • Local Institution - 0088
• Ireland
  • Dublin
    • Dublin 8, Dublin, Ireland
      • Local Institution - 0026
• Italy
  • Milano, Italy, 20133
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution - 0119
• Mexico
  • Oaxaca, Mexico, 68040
    • Local Institution - 0108
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution - 0090
    • Merida, Yucatan, Mexico, 97138
      • Local Institution - 0107
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0068
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 0028
  • Groningen, Netherlands, 9713 GZ
    • Local Institution - 0027
• Norway
  • Bergen, Norway, 5021
    • Local Institution - 0065
  • Oslo, Norway, 0379
    • Local Institution - 0064
• Romania
  • Bucharest, Romania, 010991
    • Local Institution - 0055
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0054
  • Craiova, Romania, 200347
    • Local Institution - 0033
  • Iasi, Romania, 700483
    • Local Institution - 0060
  • Suceava, Romania, 720237
    • Local Institution - 0059
• Russian Federation
  • Moscow, Russian Federation, 121309
    • Local Institution - 0031
  • Ryazan, Russian Federation, 390011
    • Local Institution - 0092
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Local Institution
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0084
      • Local Institution
    • Sandton, Gauteng, South Africa, 2199
      • Local Institution - 0017
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7700
      • Local Institution
• Spain
  • A Coruna, Spain, 15009
    • Local Institution - 0040
  • Barcelona, Spain, 08035
    • Local Institution - 0116
  • Barcelona, Spain, 08036
    • Local Institution - 0039
  • Madrid, Spain, 28041
    • Local Institution - 0077
  • Marbella, Spain, 29603
    • Local Institution - 0076
  • San Sabastian Gipuzkoa, Spain, 20014
    • Local Institution - 0041
• Sweden
  • Goteborg, Sweden, 413 45
    • Local Institution - 0067
  • Lund, Sweden, 221 85
    • Local Institution - 0037
  • Stockholm, Sweden, 171 76
    • Local Institution - 0035
• Turkey
  • Adana, Turkey, 01250
    • Local Institution - 0063
  • Antalya, Turkey, 07070
    • Local Institution - 0066
  • Izmir, Turkey, 35340
    • Local Institution - 0062
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Local Institution - 0114
  • Glasgow, United Kingdom, G12 0YN
    • Local Institution - 0084
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Local Institution - 0082
  • Aberdeenshire
    • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
      • Local Institution - 0110
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution - 0086
  • Merseyside
    • Wirral, Merseyside, United Kingdom, L63 4JY
      • Local Institution - 0083
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Local Institution - 0081
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • University of Arizona Cancer Center
  • California
    • Duarte, California, United States, 91010
      • Local Institution - 0034
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine
    • Los Angeles, California, United States, 90017
      • Los Angeles Cancer Network
    • Redondo Beach, California, United States, 90277
      • Local Institution - 0098
    • Sacramento, California, United States, 95816
      • Local Institution - 0004
    • San Francisco, California, United States, 94158
      • Local Institution - 0072
    • San Luis Obispo, California, United States, 93401
      • Local Institution - 0097
    • Santa Maria, California, United States, 93454
      • Central Coast Med Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0101
  • Florida
    • Tampa, Florida, United States, 33612
      • Local Institution - 0007
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0010
    • Decatur, Georgia, United States, 30033
      • Local Institution - 0015
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0087
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Ft. Wayne Med Onco-Hema Inc
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Local Institution - 0005
    • Paducah, Kentucky, United States, 42003
      • Oncology Associated Of Western Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0001
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0071
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0042
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital, Inc
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Local Institution - 0103
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 0070
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 0008
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0006
    • Sayre, Pennsylvania, United States, 18840
      • Donald Guthrie Foundation
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 0102
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0038

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed squamous cell head and neck cancer
• Widespread (metastatic) disease, or returned after previous treatment (recurrent)
• Tumor sample must be available for analysis of PDL1 (Programmed death-ligand 1) and HPV [Human Papilloma Virus (oropharynx only)]
• Performance status ECOG 0-1 (Eastern Cooperative Oncology Group)

Exclusion Criteria:

• Previous treatment for metastatic or recurrent disease
• Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin
• Any non-squamous subtype
• Active autoimmune disease
• Positive test for hepatitis B, C or HIV (Human Immunodeficiency Virus) virus
• Previous treatment with checkpoint inhibitor drugs
• Active CNS metastases or carcinomatous meningitis

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab and Ipilimumab; Specified dose on specified days	Biological: Nivolumab; Other Names: Opdivo; Biological: Ipilimumab
Active Comparator: Nivolumab and Ipilimumab-placebo; Specified dose on specified days	Other: Placebo; Biological: Nivolumab; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.	Approximately up to 30 months (from FPFV to Data base lock)
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Approximately up to 30 months (from FPFV to Data base lock)
Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Approximately up to 30 months (from FPFV to Data base lock)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	ORR is defined as percentage of participants with a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.	From randomization to disease progression or death. Approximately 63 Months
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Overall Survival (OS)	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.	From randomization to death. Approximately 63 Months
Overall Survival (OS) - Platinum Refractory Subgroup	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.	From randomization to death. Approximately 63 Months
Overall Survival (OS) - Platinum Eligible Subgroup	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.	From randomization to death. Approximately 63 Months
ORR - Platinum Eligible Subgroup Based on HPV p-16 Status	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
ORR - Platinum Refractory Subgroup Based on HPV p-16 Status	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.	From randomization to disease progression or death. Approximately 63 Months
Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb	From randomization to disease progression or death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status	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.	From randomization to death. Approximately 63 Months
Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	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. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb	From randomization to death. Approximately 63 Months
Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status	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.	From randomization to death. Approximately 63 Months
Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	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. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb	From randomization to death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
ORR - Platinum Refractory Subgroup Based on PD-L1 Expression	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay	From randomization to death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status	The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months
ORR - Platinum Eligible Subgroup Based on PD-L1 Expression	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization to end of study. Approximately 63 Months
Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay	From randomization to death. Approximately 63 Months
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status	The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From randomization to disease progression or death. Approximately 63 Months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2016
• Primary Completion (Actual): January 23, 2019
• Study Completion (Actual): April 21, 2022

Study Registration Dates

• First Submitted: July 1, 2016
• First Submitted That Met QC Criteria: July 1, 2016
• First Posted (Estimate): July 6, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-714; 2016-001645-64 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No