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)

• ClinicalTrials.gov Identifier: NCT02741570
• Recruitment Status: Completed
• First Posted: April 18, 2016
• Results First Posted: May 3, 2022
• Last Update Posted: October 20, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: April 13, 2016
• First Posted Date: April 18, 2016
• Results First Submitted Date: April 6, 2022
• Results First Posted Date: May 3, 2022
• Last Update Posted Date: October 20, 2022
• Actual Study Start Date: October 5, 2016
• Actual Primary Completion Date: May 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2022)

• 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)
• 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)

Original Primary Outcome Measures (submitted: April 14, 2016)

• Overall Survival (OS) [ Time Frame: Approximately 36 months ]
• Progression Free Survival (PFS) [ Time Frame: Approximately 36 months ]

Current Secondary Outcome Measures (submitted: April 6, 2022)

• 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 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)
• Progression Free Survival (PFS) [ Time Frame: From randomization to disease progression or death (Up to approximately 55 months) ]
  The time from randomization to disease progression, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or, if there is no documented progression, death based on the Blinded Independent Central Review (BICR) assessment. 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).
• Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 55 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), divided by the number randomized in the population. 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.
• Duration of Objective Response (DOR) [ Time Frame: From randomization up to approximately 55 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.

Original Secondary Outcome Measures (submitted: April 14, 2016)

• Objective Response Rate (ORR) [ Time Frame: Approximately 36 months ]
• Time to deterioration by using the 10-item Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) Symptom Index (FHNSI-10) [ Time Frame: Approximately 36 months ]
• PD-L1 expression as a predictive biomarker for efficacy [ Time Frame: Approximately 36 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Cancer

Intervention

• Biological: Nivolumab
  Other Names:

  • BMS-936558
  • Opdivo
• Biological: Ipilimumab
  Other Names:

  • BMS-734016
  • Yervoy
• Drug: Cetuximab/Erbitux
• Drug: Cisplatin/Platinol
• Drug: Carboplatin/Paraplatin
• Drug: Fluorouracil/Adrucil

Study Arms

• Experimental: Nivolumab and Ipilimumab
  Specified dose on specified days
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Active Comparator: Extreme Regimen
  Specified dose on specified days
  Interventions:

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

• Publications *: 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. Erratum In: Lancet Oncol. 2021 Apr;22(4):e134.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2019): 947
• Original Estimated Enrollment (submitted: April 14, 2016): 460
• Actual Study Completion Date: September 22, 2022
• Actual Primary Completion Date: May 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Brazil, France, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02741570
• Other Study ID Numbers: CA209-651; 2016-000725-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Ono Pharmaceutical Co. Ltd

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2022