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Head and Neck CancerPhase 3CheckMate 651NCT02741570

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

A Phase 3 study testing Nivolumab, Ipilimumab and Cetuximab/Erbitux in people with Head and Neck Cancer, run by Bristol-Myers Squibb at 133 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
Nivolumab, Ipilimumab and Cetuximab/Erbitux
Could I receive a placebo?
No, everyone receives an active treatment
How many people
947 participants
Where
133 sitesin 18 countries
Study dates
5 Oct 2016to 22 Sep 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

133 sites in 18 countries.

133 sites in 18 countries

United States22 sites

  • Local Institution - 0004

    Ann Arbor, Michigan, 48109

  • Local Institution - 0111

    Atlanta, Georgia, 30322

  • Local Institution - 0001

    Boston, Massachusetts, 02215

  • Local Institution - 0080

    Boston, Massachusetts, 02215

  • Local Institution - 0093

    Boston, Massachusetts, 02215

  • Local Institution - 0012

    Charlotte, North Carolina, 28204

  • Local Institution - 0003

    Charlottesville, Virginia, 22908

  • Local Institution - 0006

    Chicago, Illinois, 60637

  • Local Institution - 0007

    Columbus, Ohio, 43210

  • Local Institution - 0139

    Dallas, Texas, 75390

  • Local Institution - 0135

    Duarte, California, 91010

  • Local Institution - 0011

    Fairfax, Virginia, 22301

  • Local Institution - 0009

    Houston, Texas, 77030

  • Local Institution - 0014

    Houston, Texas, 77030

  • Local Institution - 0028

    Jacksonville, Florida, 32204

  • Local Institution - 0010

    Langhorne, Pennsylvania, 19047

  • Local Institution - 0125

    Morgantown, West Virginia, 26506-9162

  • Local Institution - 0015

    Philadelphia, Pennsylvania, 19107

  • Local Institution - 0013

    Pittsburgh, Pennsylvania, 15232

  • Local Institution - 0005

    Stanford, California, 94305

  • Local Institution - 0008

    Tampa, Florida, 33612

  • Local Institution - 0134

    Tucson, Arizona, 85724-5024

Other trials in United States

Japan19 sites

  • Local Institution - 0107

    Akashi-shi, Hyōgo, 6738558

  • Local Institution - 0153

    Bunkyo-ku, Tokyo, 1138519

  • Local Institution - 0101

    Chuo-ku, Tokyo, 1040045

  • Local Institution - 0113

    Fukuoka, Fukuoka, 8108563

  • Local Institution - 0152

    Isehara, Kanagawa, 2591193

  • Local Institution - 0100

    Kashiwa, Chiba, 277-8577

  • Local Institution - 0109

    Kita-gun, 7610793

  • Local Institution - 0149

    Kitaadachi-gun, Saitama, 3620806

  • Local Institution - 0102

    Kobe, Hyōgo, 650-0017

  • Local Institution - 0104

    Koto-ku, Tokyo, 135-8550

  • Local Institution - 0106

    Nagoya, Aichi-ken, 4648681

  • Local Institution - 0151

    Natori-shi, Miyagi, 9811293

  • Local Institution - 0146

    Osakasayaha, Osaka, 5898511

  • Local Institution - 0105

    Sapporo, Hokkaido, 0608648

  • Local Institution - 0108

    Sendai, Miyagi, 9808574

  • Local Institution

    Shimotsuke-shi, Tochigi, 3290498

  • Local Institution - 0114

    Sunto-gun, Shizuoka, 4118777

  • Local Institution - 0099

    Takatsuki-shi, Osaka, 5698686

  • Local Institution - 0150

    Yokohama, Kanagawa, 2360004

Other trials in Japan

France13 sites

  • Local Institution - 0133

    Amiens, Somme, 80054

  • Local Institution - 0094

    Bordeaux, 33075

  • Local Institution - 0140

    La Tronche, 38700

  • Local Institution - 0090

    Lille, 59000

  • Local Institution - 0138

    Lyon, 69004

  • Local Institution - 0054

    Lyon, 69373

  • Local Institution - 0126

    Marseille, 13005

  • Local Institution - 0055

    Nice, 06189

  • Local Institution - 0039

    Paris, 75005

  • Local Institution - 0088

    Paris, 75020

  • Local Institution

    Paris, 75908

  • Local Institution - 0089

    Strasbourg, 67200

  • Local Institution - 0040

    Villejuif, 94805

Other trials in France

Australia10 sites

  • Local Institution - 0142

    Blacktown, New South Wales, 2148

  • Local Institution - 0077

    Brisbane, Queensland, 4102

  • Local Institution - 0022

    Clayton, Victoria, 3168

  • Local Institution - 0127

    Darlinghurst, New South Wales, 2010

  • Local Institution - 0036

    Douglas, Queensland, 4814

  • Local Institution - 0021

    Elizabeth Vale, South Australia, 5112

  • Local Institution - 0128

    Gosford, New South Wales, 2250

  • Local Institution - 0131

    Melbourne, Victoria, 3000

  • Local Institution - 0020

    Nedlands, Western Australia, 6009

  • Local Institution - 0019

    St Leonards, New South Wales, 2065

Other trials in Australia

Germany10 sites

  • Local Institution - 0068

    Bonn, 53127

  • Local Institution - 0078

    Freiburg im Breisgau, 79106

  • Local Institution - 0067

    Hamburg, 20246

  • Local Institution - 0092

    Hanover, 30625

  • Local Institution - 0079

    Heidelberg, 69120

  • Local Institution - 0074

    Leipzig, 04103

  • Local Institution - 0070

    Mainz, 55131

  • Local Institution - 0065

    München, 81675

  • Local Institution - 0069

    Ulm, 89081

  • Local Institution - 0066

    Würzburg, 97070

Other trials in Germany

Italy9 sites

  • Local Institution - 0044

    Cuneo, 12100

  • IRST Meldola

    Meldola (FC), 47014

  • Local Institution - 0042

    Milan, MI, 20133

  • Azienda Ospedaliera Universitaria Di Modena

    Modena, 41124

  • Aorn Dei Colli

    Naples, 80131

  • Istituto Nazionale Tumori Fondazione Pascale

    Naples, 80131

  • Azienda Ospedaliera Di Perugia

    Perugia, 06132

  • Fondazione Policlinico Universitario A. Gemelli

    Roma, 00168

  • Local Institution - 0043

    Torino, TO, 10126

Other trials in Italy

Brazil8 sites

  • Local Institution - 0117

    Barretos, São Paulo, 14784-400

  • Local Institution - 0148

    Belo Horizonte, Minas Gerais, 30130-090

  • Local Institution - 0121

    Ijuí, Rio Grande do Sul, 98700-000

  • Local Institution - 0122

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Local Institution - 0120

    Porto Alegre, Rio Grande do Sul, 90610000

  • Local Institution - 0123

    Sao Jose de Rio Preto, São Paulo, 15091-000

  • Local Institution - 0118

    São Paulo, 01246-000

  • Local Institution - 0124

    São Paulo, 04039-004

Other trials in Brazil

United Kingdom7 sites

  • Local Institution - 0050

    Birmingham, West Midlands, B15 2TH

  • Local Institution - 0045

    London, Greater London, SW3 6JJ

  • Local Institution - 0046

    Manchester, Greater Manchester, M20 4BX

  • Local Institution - 0049

    Newcastle upon Tyne, Durham, NE4 6BE

  • Local Institution - 0132

    Sheffield, S10 2SJ

  • Local Institution - 0047

    Southampton, Hampshire, SO16 6YD

  • Local Institution - 0091

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Mexico6 sites

  • Local Institution - 0032

    León, Guanajuato, 37000

  • Local Institution - 0034

    Mexico City, Mexico City, 03100

  • Local Institution - 0030

    Mexico City, Mexico City, 14000

  • Local Institution - 0033

    Monterrey, Nuevo León, 64320

  • Local Institution - 0031

    Morelia, Michoacán, 58000

  • Local Institution - 0035

    Oaxaca City, 68000

Other trials in Mexico

Spain6 sites

  • Local Institution - 0083

    Barcelona, 08035

  • Local Institution - 0130

    L'Hospitalet Del Llobregat, 08908

  • Local Institution - 0085

    Madrid, 28034

  • Local Institution - 0082

    Madrid, 28041

  • Local Institution - 0084

    Seville, 41013

  • Local Institution - 0081

    Valencia, 46026

Other trials in Spain

Israel5 sites

  • Local Institution - 0062

    Haifa, 31096

  • Local Institution - 0060

    Jerusalem, 91120

  • Local Institution - 0063

    Petah Tikva, 49100

  • Local Institution - 0061

    Ramat Gan, 52621

  • Local Institution - 0064

    Tel Aviv, 64239

Other trials in Israel

Poland5 sites

  • Local Institution - 0037

    Bydgoszcz, 85-796

  • Local Institution - 0023

    Gdansk, 80-952

  • Local Institution - 0129

    Gliwice, 44-101

  • Local Institution - 0026

    Krakow, 31-826

  • Local Institution - 0025

    Warsaw, 02-781

Other trials in Poland

Greece3 sites

  • Local Institution - 0018

    Athens, 15123

  • Local Institution - 0017

    Nea Kifissia, 14564

  • Local Institution - 0051

    Thessaloniki, 54007

Other trials in Greece

South Korea3 sites

  • Local Institution - 0096

    Gangnam-gu, 06351

  • Local Institution - 0110

    Seoul, 05505

  • Local Institution - 0095

    Seoul, 06591

Other trials in South Korea

Austria2 sites

  • Local Institution - 0075

    Linz, 4010

  • Local Institution - 0071

    Vienna, 1090

Other trials in Austria

Switzerland2 sites

  • Local Institution - 0072

    Basel, 4031

  • Local Institution - 0073

    Zurich, 8091

Other trials in Switzerland

Taiwan2 sites

  • Local Institution - 0097

    Taichung, 40705

  • Local Institution - 0098

    Taipei, 10002

Other trials in Taiwan

Ireland1 site

  • Local Institution - 0147

    Dublin, Dublin

Other trials in Ireland

About this study

Official title: 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

Being tested
Nivolumab, Ipilimumab, Cetuximab/Erbitux, Cisplatin/Platinol, Carboplatin/Paraplatin
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called BMS-936558, Opdivo

  • IpilimumabBiological

    Also called BMS-734016, Yervoy

  • Cetuximab/ErbituxDrug

  • Cisplatin/PlatinolDrug

  • Carboplatin/ParaplatinDrug

  • Fluorouracil/AdrucilDrug

Study groups in NCT02741570
Study groupRoleWhat they receive
Nivolumab and IpilimumabExperimentalSpecified dose on specified days
Receives: Biological: Nivolumab; Biological: Ipilimumab
Extreme RegimenActive comparatorSpecified dose on specified days
Receives: Drug: Cetuximab/Erbitux; Drug: Cisplatin/Platinol; Drug: Carboplatin/Paraplatin; Drug: Fluorouracil/Adrucil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20

    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)

    Measured: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

  2. Overall Survival (OS) in All Randomized Participants

    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)

    Measured: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

Secondary outcomes (4)

  1. Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1

    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)

    Measured: From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)

  2. Progression Free Survival (PFS)

    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).

    Measured: From randomization to disease progression or death (Up to approximately 65 months)

  3. Objective Response Rate (ORR)

    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.

    Measured: From randomization up to approximately 65 months

  4. Duration of Objective Response (DOR)

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2016 (estimated)
  2. Study start5 Oct 2016
  3. Primary completion10 May 2021
  4. Study completion22 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
947 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02741570
Sponsor's protocol ID
CA209-651
Other IDs
2016-000725-39, 2016
Acronym
CheckMate 651
Status last verified
Aug 2023
First submitted
13 Apr 2016
Last updated
21 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Haddad RI, Harrington K, Tahara M, Ferris RL, Gillison M, Fayette J, Daste A, Koralewski P, Zurawski B, Taberna M, Saba NF, Mak M, Kawecki A, Girotto G, Alvarez Avitia MA, Even C, Toledo JGR, Guminski A, Muller-Richter U, Kiyota N, Roberts M, Khan TA, Miller-Moslin K, Wei L, Argiris A. Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651. J Clin Oncol. 2023 Apr 20;41(12):2166-2180. doi: 10.1200/JCO.22.00332. Epub 2022 Dec 6.

    PubMed 36473143

  • Hwang M, Seiwert TY. Are taxanes the future for head and neck cancer? Pragmatism in the immunotherapy era. Lancet Oncol. 2021 Apr;22(4):413-415. doi: 10.1016/S1470-2045(21)00121-2. Epub 2021 Mar 5. No abstract available.

    PubMed 33684371

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab, Ipilimumab and Cetuximab/Erbitux in people with Head and Neck Cancer, run by Bristol-Myers Squibb at 133 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 133 sites in United States, Japan, France, Australia, Germany and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02741570, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.

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