Last reviewed · How we verify

NCT02741570: CheckMate 651

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

Completed Phase 3 Results posted Last updated 21 September 2023
What this trial tests

Phase 3 trial testing Nivolumab in Head and Neck Cancer in 947 participants. Completed in 22 September 2022.

Timeline
5 October 2016
Primary endpoint
10 May 2021
22 September 2022

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment947
Start date5 October 2016
Primary completion10 May 2021
Estimated completion22 September 2022
Sites133 locations across France, Italy, Japan, Greece, Austria, Taiwan, Ireland, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Head and Neck Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Nivolumab + Ipilimumab17.5813.77 – 21.98
EXTREME Regimen14.5912.32 – 15.97
Overall Survival (OS) in All Randomized Participants Primary · 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)

GroupValue95% CI
Nivolumab + Ipilimumab13.9012.12 – 15.77
EXTREME Regimen13.5012.55 – 15.21
Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1 Secondary · 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)

GroupValue95% CI
Nivolumab + Ipilimumab15.6713.70 – 18.79
EXTREME Regimen13.2411.07 – 14.59
Progression Free Survival (PFS) Secondary · 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-

Randomized participants
GroupValue95% CI
Nivolumab + Ipilimumab3.292.83 – 4.17
EXTREME Regimen6.775.78 – 7.00
Randomized PD-L1 CPS >= 20 participants
GroupValue95% CI
Nivolumab + Ipilimumab5.393.09 – 6.93
EXTREME Regimen6.975.78 – 8.67
Objective Response Rate (ORR) Secondary · 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.

All randomized participants
GroupValue95% CI
Nivolumab + Ipilimumab24.220.4 – 28.3
EXTREME Regimen37.132.7 – 41.6
Randomized PD-L1 CPS >= 20 participants
GroupValue95% CI
Nivolumab + Ipilimumab34.127.3 – 41.4
EXTREME Regimen35.428.4 – 42.9
Duration of Objective Response (DOR) Secondary · 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.

All randomized participants
GroupValue95% CI
Nivolumab + Ipilimumab16.599.69 – 29.40
EXTREME Regimen5.885.45 – 6.97
Randomized PD-L1 CPS >= 20 participants
GroupValue95% CI
Nivolumab + Ipilimumab33.5112.12 – NA
EXTREME Regimen6.975.65 – 10.12
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20 - Extended Collection Secondary · 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)

GroupValue95% CI
Nivolumab + Ipilimumab17.7413.77 – 21.98
EXTREME Regimen14.5912.32 – 15.97
Overall Survival (OS) in All Randomized Participants - Extended Collection Secondary · 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)

GroupValue95% CI
Nivolumab + Ipilimumab13.9012.12 – 15.77
EXTREME Regimen13.5012.48 – 15.11

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality was assessed from participants first dose to their study completion (up to approximately 65 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 63 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab + Ipilimumab
Serious: 313/468 (67%)
Deaths: 388/472
EXTREME Regimen
Serious: 290/441 (66%)
Deaths: 406/475

Serious adverse events (382 terms)

ReactionSystemNivolumab + IpilimumabEXTREME Regimen
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
Tumour haemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnaemiaBlood and lymphatic system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ColitisGastrointestinal disorders
DysphagiaGastrointestinal disorders
SepsisInfections and infestations
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
Sudden deathGeneral disorders
Pneumonia aspirationInfections and infestations
Mucosal inflammationGeneral disorders
DehydrationMetabolism and nutrition disorders
HypercalcaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
StomatitisGastrointestinal disorders
General physical health deteriorationGeneral disorders
CellulitisInfections and infestations
Electrolyte imbalanceMetabolism and nutrition disorders
Other adverse events (64 terms — click to expand)

ReactionSystemNivolumab + IpilimumabEXTREME Regimen
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
RashSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
HypomagnesaemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
Mucosal inflammationGeneral disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
StomatitisGastrointestinal disorders
ParonychiaInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Weight decreasedInvestigations
Dry skinSkin and subcutaneous tissue disorders
Neutrophil count decreasedInvestigations
Skin fissuresSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Platelet count decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DysphagiaGastrointestinal disorders
Lipase increasedInvestigations
PyrexiaGeneral disorders
HypocalcaemiaMetabolism and nutrition disorders
PneumoniaInfections and infestations
HyperthyroidismEndocrine disorders
AlopeciaSkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Neck painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Abdominal painGastrointestinal disorders
White blood cell count decreasedInvestigations

Most-reported serious reactions: Malignant neoplasm progression, Pneumonia, Febrile neutropenia, Tumour haemorrhage, Anaemia, Dyspnoea, Colitis, Dysphagia.

Data from ClinicalTrials.gov NCT02741570 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC).
    Cohen EEW, Bell RB, Bifulco CB, Burtness B, et al · · 2019 · cited 528× · PMID 31307547 · DOI 10.1186/s40425-019-0662-5
  3. Immunotherapy for head and neck cancer: Recent advances and future directions.
    Cramer JD, Burtness B, Ferris RL. · · 2019 · cited 238× · PMID 31683169 · DOI 10.1016/j.oraloncology.2019.104460
  4. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
    Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
  5. Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma.
    Mei Z, Huang J, Qiao B, Lam AK. · · 2020 · cited 197× · PMID 32461587 · DOI 10.1038/s41368-020-0084-8
  6. The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?
    Franzin R, Netti GS, Spadaccino F, Porta C, et al · · 2020 · cited 142× · PMID 33162990 · DOI 10.3389/fimmu.2020.574271
  7. 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.
    Haddad RI, Harrington K, Tahara M, Ferris RL, et al · · 2023 · cited 125× · PMID 36473143 · DOI 10.1200/jco.22.00332
  8. Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy.
    Bhat AA, Yousuf P, Wani NA, Rizwan A, et al · · 2021 · cited 119× · PMID 33436555 · DOI 10.1038/s41392-020-00419-w

Verify or expand the search:

Other trials of Nivolumab

Trials testing the same drug.

Other recruiting trials for Head and Neck Cancer

Currently open trials in the same condition.

Other Bristol-Myers Squibb trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02741570.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing