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

NCT02741570 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-6512016-000725-39
• Study Type: interventional
• Target: 947
• Locations: 17 countries
• Sites: 131

Brief 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

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• 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)

  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

  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 Outcomes (4)

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

  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)

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

• Objective Response Rate (ORR)

  From randomization up to approximately 65 months

• Duration of Objective Response (DOR)

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

Study Arms (2)

Nivolumab and Ipilimumab

EXPERIMENTAL

Specified dose on specified days

Biological: Nivolumab; Biological: Ipilimumab

Extreme Regimen

ACTIVE COMPARATOR

Specified dose on specified days

Drug: Cetuximab/Erbitux; Drug: Cisplatin/Platinol; Drug: Carboplatin/Paraplatin; Drug: Fluorouracil/Adrucil

Interventions

Nivolumab BIOLOGICAL

Also known as: BMS-936558, Opdivo

Nivolumab and Ipilimumab

Ipilimumab BIOLOGICAL

Also known as: BMS-734016, Yervoy

Nivolumab and Ipilimumab

Cetuximab/Erbitux DRUG

Extreme Regimen

Cisplatin/Platinol DRUG

Extreme Regimen

Carboplatin/Paraplatin DRUG

Extreme Regimen

Fluorouracil/Adrucil DRUG

Extreme Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (133)

Local Institution - 0134

Tucson, Arizona, 85724-5024, United States

Location

Local Institution - 0135

Duarte, California, 91010, United States

Location

Local Institution - 0005

Stanford, California, 94305, United States

Location

Local Institution - 0028

Jacksonville, Florida, 32204, United States

Location

Local Institution - 0008

Tampa, Florida, 33612, United States

Location

Local Institution - 0111

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0006

Chicago, Illinois, 60637, United States

Location

Local Institution - 0001

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0080

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0093

Boston, Massachusetts, 02215, United States

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Local Institution - 0004

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0012

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0007

Columbus, Ohio, 43210, United States

Location

Local Institution - 0010

Langhorne, Pennsylvania, 19047, United States

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Local Institution - 0015

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 0013

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 0139

Dallas, Texas, 75390, United States

Location

Local Institution - 0009

Houston, Texas, 77030, United States

Location

Local Institution - 0014

Houston, Texas, 77030, United States

Location

Local Institution - 0003

Charlottesville, Virginia, 22908, United States

Location

Local Institution - 0011

Fairfax, Virginia, 22301, United States

Location

Local Institution - 0125

Morgantown, West Virginia, 26506-9162, United States

Location

Local Institution - 0142

Blacktown, New South Wales, 2148, Australia

Location

Local Institution - 0127

Darlinghurst, New South Wales, 2010, Australia

Location

Local Institution - 0128

Gosford, New South Wales, 2250, Australia

Location

Local Institution - 0019

St Leonards, New South Wales, 2065, Australia

Location

Local Institution - 0077

Brisbane, Queensland, 4102, Australia

Location

Local Institution - 0036

Douglas, Queensland, 4814, Australia

Location

Local Institution - 0021

Elizabeth Vale, South Australia, 5112, Australia

Location

Local Institution - 0022

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0131

Melbourne, Victoria, 3000, Australia

Location

Local Institution - 0020

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0075

Linz, 4010, Austria

Location

Local Institution - 0071

Vienna, 1090, Austria

Location

Local Institution - 0148

Belo Horizonte, Minas Gerais, 30130-090, Brazil

Location

Local Institution - 0121

Ijuí, Rio Grande do Sul, 98700-000, Brazil

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Local Institution - 0122

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Local Institution - 0120

Porto Alegre, Rio Grande do Sul, 90610000, Brazil

Location

Local Institution - 0117

Barretos, São Paulo, 14784-400, Brazil

Location

Local Institution - 0123

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

Location

Local Institution - 0118

São Paulo, 01246-000, Brazil

Location

Local Institution - 0124

São Paulo, 04039-004, Brazil

Location

Local Institution - 0133

Amiens, Somme, 80054, France

Location

Local Institution - 0094

Bordeaux, 33075, France

Location

Local Institution - 0140

La Tronche, 38700, France

Location

Local Institution - 0090

Lille, 59000, France

Location

Local Institution - 0138

Lyon, 69004, France

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Local Institution - 0054

Lyon, 69373, France

Location

Local Institution - 0126

Marseille, 13005, France

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Local Institution - 0055

Nice, 06189, France

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Local Institution - 0039

Paris, 75005, France

Location

Local Institution - 0088

Paris, 75020, France

Location

Local Institution

Paris, 75908, France

Location

Local Institution - 0089

Strasbourg, 67200, France

Location

Local Institution - 0040

Villejuif, 94805, France

Location

Local Institution - 0068

Bonn, 53127, Germany

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Local Institution - 0078

Freiburg im Breisgau, 79106, Germany

Location

Local Institution - 0067

Hamburg, 20246, Germany

Location

Local Institution - 0092

Hanover, 30625, Germany

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Local Institution - 0079

Heidelberg, 69120, Germany

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Local Institution - 0074

Leipzig, 04103, Germany

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Local Institution - 0070

Mainz, 55131, Germany

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Local Institution - 0065

München, 81675, Germany

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Local Institution - 0069

Ulm, 89081, Germany

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Local Institution - 0066

Würzburg, 97070, Germany

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Local Institution - 0018

Athens, 15123, Greece

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Local Institution - 0017

Nea Kifissia, 14564, Greece

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Local Institution - 0051

Thessaloniki, 54007, Greece

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Local Institution - 0147

Dublin, Dublin, Ireland

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Local Institution - 0062

Haifa, 31096, Israel

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Local Institution - 0060

Jerusalem, 91120, Israel

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Local Institution - 0063

Petah Tikva, 49100, Israel

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Local Institution - 0061

Ramat Gan, 52621, Israel

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Local Institution - 0064

Tel Aviv, 64239, Israel

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Local Institution - 0042

Milan, MI, 20133, Italy

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Local Institution - 0043

Torino, TO, 10126, Italy

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Local Institution - 0044

Cuneo, 12100, Italy

Location

IRST Meldola

Meldola (FC), 47014, Italy

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Azienda Ospedaliera Universitaria Di Modena

Modena, 41124, Italy

Location

Aorn Dei Colli

Napoli, 80131, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale

Napoli, 80131, Italy

Location

Azienda Ospedaliera Di Perugia

Perugia, 06132, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Local Institution - 0106

Nagoya, Aichi-ken, 4648681, Japan

Location

Local Institution - 0100

Kashiwa, Chiba, 277-8577, Japan

Location

Local Institution - 0113

Fukuoka, Fukuoka, 8108563, Japan

Location

Local Institution - 0105

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 0107

Akashi-shi, Hyōgo, 6738558, Japan

Location

Local Institution - 0102

Kobe, Hyōgo, 650-0017, Japan

Location

Local Institution - 0152

Isehara, Kanagawa, 2591193, Japan

Location

Local Institution - 0150

Yokohama, Kanagawa, 2360004, Japan

Location

Local Institution - 0151

Natori-shi, Miyagi, 9811293, Japan

Location

Local Institution - 0108

Sendai, Miyagi, 9808574, Japan

Location

Local Institution - 0146

Osakasayaha, Osaka, 5898511, Japan

Location

Local Institution - 0099

Takatsuki-shi, Osaka, 5698686, Japan

Location

Local Institution - 0149

Kitaadachi-gun, Saitama, 3620806, Japan

Location

Local Institution - 0114

Sunto-gun, Shizuoka, 4118777, Japan

Location

Local Institution

Shimotsuke-shi, Tochigi, 3290498, Japan

Location

Local Institution - 0153

Bunkyo-ku, Tokyo, 1138519, Japan

Location

Local Institution - 0101

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0104

Koto-ku, Tokyo, 135-8550, Japan

Location

Local Institution - 0109

Kita-gun, 7610793, Japan

Location

Local Institution - 0032

León, Guanajuato, 37000, Mexico

Location

Local Institution - 0034

Mexico City, Mexico City, 03100, Mexico

Location

Local Institution - 0030

Mexico City, Mexico City, 14000, Mexico

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Local Institution - 0031

Morelia, Michoacán, 58000, Mexico

Location

Local Institution - 0033

Monterrey, Nuevo León, 64320, Mexico

Location

Local Institution - 0035

Oaxaca City, 68000, Mexico

Location

Local Institution - 0037

Bydgoszcz, 85-796, Poland

Location

Local Institution - 0023

Gdansk, 80-952, Poland

Location

Local Institution - 0129

Gliwice, 44-101, Poland

Location

Local Institution - 0026

Krakow, 31-826, Poland

Location

Local Institution - 0025

Warsaw, 02-781, Poland

Location

Local Institution - 0096

Gangnam-gu, 06351, South Korea

Location

Local Institution - 0110

Seoul, 05505, South Korea

Location

Local Institution - 0095

Seoul, 06591, South Korea

Location

Local Institution - 0083

Barcelona, 08035, Spain

Location

Local Institution - 0130

L'Hospitalet Del Llobregat, 08908, Spain

Location

Local Institution - 0085

Madrid, 28034, Spain

Location

Local Institution - 0082

Madrid, 28041, Spain

Location

Local Institution - 0084

Seville, 41013, Spain

Location

Local Institution - 0081

Valencia, 46026, Spain

Location

Local Institution - 0072

Basel, 4031, Switzerland

Location

Local Institution - 0073

Zurich, 8091, Switzerland

Location

Local Institution - 0097

Taichung, 40705, Taiwan

Location

Local Institution - 0098

Taipei, 10002, Taiwan

Location

Local Institution - 0049

Newcastle upon Tyne, Durham, NE4 6BE, United Kingdom

Location

Local Institution - 0045

London, Greater London, SW3 6JJ, United Kingdom

Location

Local Institution - 0046

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0047

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Local Institution - 0091

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Local Institution - 0050

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Local Institution - 0132

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36473143 DERIVED

• 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.

  PMID: 33684371 DERIVED

Related Links

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

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Nivolumab; Ipilimumab; Cetuximab; Cisplatin; Carboplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: April 18, 2016
• Study Start: October 5, 2016
• Primary Completion: May 10, 2021
• Study Completion: September 22, 2022
• Last Updated: September 21, 2023
• Results First Posted: May 3, 2022

Record last verified: 2023-08

Locations

CH (2); GB (7); IL (5); DE (10); FR (13); US (22); AU (10); PL (5); IE (1); JP (19); KR (3); GR (3); BR (8); TW (2); ME (6); IT (9); ES (6)