Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (CheckMate 651)

August 31, 2023 updated by: Bristol-Myers Squibb

An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen (Cetuximab + Cisplatin/Carboplatin + Fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

The main purpose of this study is to compare nivolumab and ipilimumab with the extreme regimen as first line treatment in patients with recurrent or metastatic squamous cell of the head and neck cancer

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

947

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
        • Local Institution - 0142
      • Darlinghurst, New South Wales, Australia, 2010
        • Local Institution - 0127
      • Gosford, New South Wales, Australia, 2250
        • Local Institution - 0128
      • St. Leonards, New South Wales, Australia, 2065
        • Local Institution - 0019
    • Queensland
      • Brisbane, Queensland, Australia, 4102
        • Local Institution - 0077
      • Douglas, Queensland, Australia, 4814
        • Local Institution - 0036
    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Local Institution - 0021
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Local Institution - 0022
      • Melbourne, Victoria, Australia, 3000
        • Local Institution - 0131
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Local Institution - 0020
  • Austria
      • Linz, Austria, 4010
        • Local Institution - 0075
      • Wien, Austria, 1090
        • Local Institution - 0071
  • Brazil
      • Sao Paulo, Brazil, 01246-000
        • Local Institution - 0118
      • Sao Paulo, Brazil, 04039-004
        • Local Institution - 0124
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30130-090
        • Local Institution - 0148
    • RIO Grande DO SUL
      • Ijui, RIO Grande DO SUL, Brazil, 98700-000
        • Local Institution - 0121
      • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
        • Local Institution - 0122
      • Porto Alegre, RIO Grande DO SUL, Brazil, 90610000
        • Local Institution - 0120
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil, 14784-400
        • Local Institution - 0117
      • Sao Jose De Rio Preto, Sao Paulo, Brazil, 15091-000
        • Local Institution - 0123
  • France
      • Bordeaux, France, 33075
        • Local Institution - 0094
      • La Tronche, France, 38700
        • Local Institution - 0140
      • Lille, France, 59000
        • Local Institution - 0090
      • Lyon, France, 69004
        • Local Institution - 0138
      • Lyon, France, 69373
        • Local Institution - 0054
      • Marseille, France, 13005
        • Local Institution - 0126
      • Nice Cedex 2, France, 06189
        • Local Institution - 0055
      • Paris, France, 75005
        • Local Institution - 0039
      • Paris, France, 75020
        • Local Institution - 0088
      • Paris, France, 75908
        • Local Institution
      • Strasbourg, France, 67200
        • Local Institution - 0089
      • Villejuif Cedex, France, 94805
        • Local Institution - 0040
    • Somme
      • Amiens, Somme, France, 80054
        • Local Institution - 0133
  • Germany
      • Bonn, Germany, 53127
        • Local Institution - 0068
      • Freiburg, Germany, 79106
        • Local Institution - 0078
      • Hamburg, Germany, 20246
        • Local Institution - 0067
      • Hannover, Germany, 30625
        • Local Institution - 0092
      • Heidelberg, Germany, 69120
        • Local Institution - 0079
      • Leipzig, Germany, 04103
        • Local Institution - 0074
      • Mainz, Germany, 55131
        • Local Institution - 0070
      • Muenchen, Germany, 81675
        • Local Institution - 0065
      • Ulm, Germany, 89081
        • Local Institution - 0069
      • Wuerzburg, Germany, 97070
        • Local Institution - 0066
  • Greece
      • Athens, Greece, 15123
        • Local Institution - 0018
      • Nea Kifissia, Greece, 14564
        • Local Institution - 0017
      • Thessaloniki, Greece, 54007
        • Local Institution - 0051
  • Ireland
    • Dublin
      • Dublin 8, Dublin, Ireland
        • Local Institution - 0147
  • Israel
      • Haifa, Israel, 31096
        • Local Institution - 0062
      • Jerusalem, Israel, 91120
        • Local Institution - 0060
      • Petah-tikva, Israel, 49100
        • Local Institution - 0063
      • Ramat-gan, Israel, 52621
        • Local Institution - 0061
      • Tel-Aviv, Israel, 64239
        • Local Institution - 0064
  • Italy
      • Cuneo, Italy, 12100
        • Local Institution - 0044
      • Meldola (fc), Italy, 47014
        • IRST Meldola
      • Modena, Italy, 41124
        • Azienda Ospedaliera Universitaria di Modena
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori Fondazione Pascale
      • Napoli, Italy, 80131
        • AORN dei Colli
      • Perugia, Italy, 06132
        • Azienda Ospedaliera di Perugia
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli
    • MI
      • Milano, MI, Italy, 20133
        • Local Institution - 0042
    • TO
      • Torino, TO, Italy, 10126
        • Local Institution - 0043
  • Japan
      • Kita-gun, Japan, 7610793
        • Local Institution - 0109
    • Aichi
      • Nagoya, Aichi, Japan, 4648681
        • Local Institution - 0106
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • Local Institution - 0100
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan, 8108563
        • Local Institution - 0113
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 0608648
        • Local Institution - 0105
    • Hyogo
      • Akashi-shi, Hyogo, Japan, 6738558
        • Local Institution - 0107
      • Kobe-shi, Hyogo, Japan, 650-0017
        • Local Institution - 0102
    • Kanagawa
      • Isehara, Kanagawa, Japan, 2591193
        • Local Institution - 0152
      • Yokohama-shi, Kanagawa, Japan, 2360004
        • Local Institution - 0150
    • Miyagi
      • Natori-shi, Miyagi, Japan, 9811293
        • Local Institution - 0151
      • Sendai-shi, Miyagi, Japan, 9808574
        • Local Institution - 0108
    • Osaka
      • Osakasayaha, Osaka, Japan, 5898511
        • Local Institution - 0146
      • Takatsuki-shi, Osaka, Japan, 5698686
        • Local Institution - 0099
    • Saitama
      • Kitaadachi-gun, Saitama, Japan, 3620806
        • Local Institution - 0149
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 4118777
        • Local Institution - 0114
    • Tochigi
      • Shimotsuke-shi, Tochigi, Japan, 3290498
        • Local Institution
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 1138519
        • Local Institution - 0153
      • Chuo-ku, Tokyo, Japan, 1040045
        • Local Institution - 0101
      • Koto-ku, Tokyo, Japan, 135-8550
        • Local Institution - 0104
  • Korea, Republic of
      • Gangnam-gu, Korea, Republic of, 06351
        • Local Institution - 0096
      • Seoul, Korea, Republic of, 05505
        • Local Institution - 0110
      • Seoul, Korea, Republic of, 06591
        • Local Institution - 0095
  • Mexico
      • Oaxaca, Mexico, 68000
        • Local Institution - 0035
    • Distrito Federal
      • Mexico, Distrito Federal, Mexico, 14000
        • Local Institution - 0030
      • Mexico City, Distrito Federal, Mexico, 03100
        • Local Institution - 0034
    • Guanajuato
      • Leon de los Aldama, Guanajuato, Mexico, 37000
        • Local Institution - 0032
    • Michoacan
      • Morelia, Michoacan, Mexico, 58000
        • Local Institution - 0031
    • Nuevo LEON
      • Monterrey, Nuevo LEON, Mexico, 64320
        • Local Institution - 0033
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Local Institution - 0037
      • Gdansk, Poland, 80-952
        • Local Institution - 0023
      • Gliwice, Poland, 44-101
        • Local Institution - 0129
      • Krakow, Poland, 31-826
        • Local Institution - 0026
      • Warszawa, Poland, 02-781
        • Local Institution - 0025
  • Spain
      • Barcelona, Spain, 08035
        • Local Institution - 0083
      • L'Hospitalet Del Llobregat, Spain, 08908
        • Local Institution - 0130
      • Madrid, Spain, 28034
        • Local Institution - 0085
      • Madrid, Spain, 28041
        • Local Institution - 0082
      • Sevilla, Spain, 41013
        • Local Institution - 0084
      • Valencia, Spain, 46026
        • Local Institution - 0081
  • Switzerland
      • Basel, Switzerland, 4031
        • Local Institution - 0072
      • Zuerich, Switzerland, 8091
        • Local Institution - 0073
  • Taiwan
      • Taichung, Taiwan, 40705
        • Local Institution - 0097
      • Taipei, Taiwan, 10002
        • Local Institution - 0098
  • United Kingdom
      • Sheffield, United Kingdom, S10 2SJ
        • Local Institution - 0132
    • Durham
      • Newcastle Upon Tyne, Durham, United Kingdom, NE4 6BE
        • Local Institution - 0049
    • Greater London
      • London, Greater London, United Kingdom, SW3 6JJ
        • Local Institution - 0045
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
        • Local Institution - 0046
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Local Institution - 0047
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Local Institution - 0091
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2TH
        • Local Institution - 0050
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724-5024
        • Local Institution - 0134
    • California
      • Duarte, California, United States, 91010
        • Local Institution - 0135
      • Stanford, California, United States, 94305
        • Local Institution - 0005
    • Florida
      • Jacksonville, Florida, United States, 32204
        • Local Institution - 0028
      • Tampa, Florida, United States, 33612
        • Local Institution - 0008
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Local Institution - 0111
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Local Institution - 0006
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0001
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0080
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0093
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Local Institution - 0004
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Local Institution - 0012
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Local Institution - 0007
    • Pennsylvania
      • Langhorne, Pennsylvania, United States, 19047
        • Local Institution - 0010
      • Philadelphia, Pennsylvania, United States, 19107
        • Local Institution - 0015
      • Pittsburgh, Pennsylvania, United States, 15232
        • Local Institution - 0013
    • Texas
      • Dallas, Texas, United States, 75390
        • Local Institution - 0139
      • Houston, Texas, United States, 77030
        • Local Institution - 0009
      • Houston, Texas, United States, 77030
        • Local Institution - 0014
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Local Institution - 0003
      • Fairfax, Virginia, United States, 22301
        • Local Institution - 0011
    • West Virginia
      • Morgantown, West Virginia, United States, 26506-9162
        • Local Institution - 0125

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx & larynx) that is not amenable to curative therapy.
  • No prior systemic cancer therapy for recurrent or metastatic disease (except if chemotherapy was part of multimodal treatment completed 6 months prior to enrolment).
  • Measurable disease detected by imaging exam (CT or MRI).
  • Have tumor tissue for PD L1 expression testing, and for oropharyngeal cancer have results from testing of HPV p16 status.

Exclusion Criteria:

  • Metastatic or recurrent carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, squamous cell carcinoma originating from skin and salivary glands or non squamous histologies (eg. mucosal melanoma).
  • No prior treatment with anti PD1, anti PD L1, anti CTLA 4 antibody or any other antibody or drugs targeting T cell costimulation or checkpoint pathways, or cetuximab or EGFR inhibitors in any treatment setting.
  • Participants with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder.
  • Inadequate hematologic, renal or hepatic function.

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nivolumab and Ipilimumab
Specified dose on specified days
Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Other Names:
  • BMS-734016
  • Yervoy
Active Comparator: Extreme Regimen
Specified dose on specified days
Drug: Cetuximab/Erbitux
Drug: Cisplatin/Platinol
Drug: Carboplatin/Paraplatin
Drug: Fluorouracil/Adrucil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20
Time Frame: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)
From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
Overall Survival (OS) in All Randomized Participants
Time Frame: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)
From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1
Time Frame: From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)
Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)
From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)
Progression Free Survival (PFS)
Time Frame: From randomization to disease progression or death (Up to approximately 65 months)

PFS is defined as the time between the date of randomization and the date of first documented tumor progression, based on Blinded Independent Central Review (BICR) assessments (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria), or death due to any cause, whichever occurs first. Participants who neither progress nor die will be censored on the date of their last tumor assessment. Participants who receive subsequent anti-cancer therapy prior to documented progression, will be censored on the date of their last tumor assessment prior to subsequent therapy. (Based on Kaplan-Meier Estimates)

Progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition 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 (Up to approximately 65 months)
Objective Response Rate (ORR)
Time Frame: From randomization up to approximately 65 months

Objective Response Rate (ORR) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by blinded independent central review (BICR) assessment.

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 up to approximately 65 months
Duration of Objective Response (DOR)
Time Frame: From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months)

The time between the first documented response (Complete response (CR) or partial response (PR)) and progression or death, per RECIST 1.1 by blinded independent central review (BICR) assessment. (Based on Kaplan-Meier Estimates)

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 the first documented response (CR or PR) and progression (up to approximately 65 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2016

Primary Completion (Actual)

May 10, 2021

Study Completion (Actual)

September 22, 2022

Study Registration Dates

First Submitted

April 13, 2016

First Submitted That Met QC Criteria

April 14, 2016

First Posted (Estimated)

April 18, 2016

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-651
  • 2016-000725-39 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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