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NCT02823574: CheckMate 714

Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Completed Phase 2 Results posted Last updated 3 May 2023
What this trial tests

Phase 2 trial testing Nivolumab in Head and Neck Cancer in 425 participants. Completed in 21 April 2022.

Timeline
8 November 2016
Primary endpoint
23 January 2019
21 April 2022

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment425
Start date8 November 2016
Primary completion23 January 2019
Estimated completion21 April 2022
Sites105 locations across Italy, Finland, Ireland, Netherlands, Russia, Belgium, Sweden, Mexico

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.

Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup Primary · Approximately up to 30 months (from FPFV to Data base lock)

ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. 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.

GroupValue95% CI
Treatment A - Platinum Refractory Subgroup13.28.4 – 19.5
Treatment B - Platinum Refractory Subgroup18.310.6 – 28.4
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup Primary · Approximately up to 30 months (from FPFV to Data base lock)

The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

GroupValue95% CI
Treatment A - Platinum Refractory SubgroupNA11.01 – NA
Treatment B - Platinum Refractory Subgroup11.074.14 – NA
Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup Primary · Approximately up to 30 months (from FPFV to Data base lock)

Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. 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.

GroupValue95% CI
Treatment A - Platinum Refractory Subgroup2.561.1 – 6.6
Treatment B - Platinum Refractory Subgroup1.511.2 – 7.7
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup Secondary · From randomization to end of study. Approximately 63 Months

ORR is defined as percentage of participants with a complete response (CR) or partial response (PR). 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.

GroupValue95% CI
Treatment A - Platinum Eligible Subgroup20.313.6 – 28.5
Treatment B - Platinum Eligible Subgroup29.518.5 – 42.6
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup Secondary · From randomization to disease progression or death. Approximately 63 Months

The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

GroupValue95% CI
Treatment A - Platinum Eligible Subgroup27.0411.01 – NA
Treatment B - Platinum Eligible Subgroup24.616.90 – NA
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup Secondary · From randomization to disease progression or death. Approximately 63 Months

The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, 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).

GroupValue95% CI
Treatment A - Platinum Refractory Subgroup2.501.45 – 2.76
Treatment B - Platinum Refractory Subgroup2.601.54 – 3.38
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup Secondary · From randomization to disease progression or death. Approximately 63 Months

the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, 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).

GroupValue95% CI
Treatment A - Platinum Eligible Subgroup2.761.64 – 4.17
Treatment B - Platinum Eligible Subgroup2.861.51 – 5.65
Overall Survival (OS) Secondary · From randomization to death. Approximately 63 Months

Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

GroupValue95% CI
Treatment A9.767.52 – 11.47
Treatment B11.308.48 – 14.00
Overall Survival (OS) - Platinum Refractory Subgroup Secondary · From randomization to death. Approximately 63 Months

Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

GroupValue95% CI
Treatment A - Platinum Refractory Subgroup9.766.51 – 11.37
Treatment B - Platinum Refractory Subgroup9.597.13 – 14.26
Overall Survival (OS) - Platinum Eligible Subgroup Secondary · From randomization to death. Approximately 63 Months

Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

GroupValue95% CI
Treatment A - Platinum Eligible Subgroup9.717.43 – 12.62
Treatment B - Platinum Eligible Subgroup12.919.33 – 22.01
ORR - Platinum Eligible Subgroup Based on HPV p-16 Status Secondary · From randomization to end of study. Approximately 63 Months

ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. 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.

Positive
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup20.08.4 – 36.9
Treatment B - Platinum Eligible Subgroup41.218.4 – 67.1
Negative
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup20.512.6 – 30.4
Treatment B - Platinum Eligible Subgroup25.013.2 – 40.3
ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker Secondary · From randomization to end of study. Approximately 63 Months

ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether targ

TMB < 7
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup10.23.8 – 20.8
Treatment B - Platinum Eligible Subgroup30.814.3 – 51.8
TMB ≥ 7
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup34.219.6 – 51.4
Treatment B - Platinum Eligible Subgroup28.611.3 – 52.2
TMB < 10
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup17.39.8 – 27.3
Treatment B - Platinum Eligible Subgroup28.614.6 – 46.3
TMB ≥ 10
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup31.311.0 – 58.7
Treatment B - Platinum Eligible Subgroup33.39.9 – 65.1
TMB Not Reported
GroupValue95% CI
Treatment A - Platinum Eligible Subgroup23.19.0 – 43.6
Treatment B - Platinum Eligible Subgroup28.68.4 – 58.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events and Serious Adverse Events: (From first dose to last dose + 100 days): Approximately 32 months All-Cause mortality (From randomization to end of study): Approximately 63 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment A - Platinum Refractory Subgroup
Serious: 103/158 (65%)
Deaths: 131/159
Treatment B - Platinum Refractory Subgroup
Serious: 52/82 (63%)
Deaths: 71/82
Treatment A - Platinum Eligible Subgroup
Serious: 89/122 (73%)
Deaths: 102/123
Treatment B - Platinum Eligible Subgroup
Serious: 35/61 (57%)
Deaths: 49/61

Serious adverse events (182 terms)

ReactionSystemTreatment A - Platinum Ref…Treatment B - Platinum Ref…Treatment A - Platinum Eli…Treatment B - Platinum Eli…
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
VomitingGastrointestinal disorders
HypercalcaemiaMetabolism and nutrition disorders
DysphagiaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Immune-mediated enterocolitisGastrointestinal disorders
General physical health deteriorationGeneral disorders
Sudden deathGeneral disorders
Pneumonia aspirationInfections and infestations
HaemoptysisRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Febrile bone marrow aplasiaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
Adrenal insufficiencyEndocrine disorders
HypophysitisEndocrine disorders
Autoimmune colitisGastrointestinal disorders
Mouth haemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
Mucosal inflammationGeneral disorders
CellulitisInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
Other adverse events (58 terms — click to expand)

ReactionSystemTreatment A - Platinum Ref…Treatment B - Platinum Ref…Treatment A - Platinum Eli…Treatment B - Platinum Eli…
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
HypothyroidismEndocrine disorders
AstheniaGeneral disorders
ConstipationGastrointestinal disorders
Weight decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
VomitingGastrointestinal disorders
HypercalcaemiaMetabolism and nutrition disorders
Neck painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
HyponatraemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Lipase increasedInvestigations
InsomniaPsychiatric disorders
LymphopeniaBlood and lymphatic system disorders
HyperthyroidismEndocrine disorders
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Dry mouthGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
Abdominal painGastrointestinal disorders
Oedema peripheralGeneral disorders
PneumoniaInfections and infestations
Amylase increasedInvestigations
Dry skinSkin and subcutaneous tissue disorders
Face oedemaGeneral disorders
Mucosal inflammationGeneral disorders
Oral candidiasisInfections and infestations
Blood alkaline phosphatase increasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Malignant neoplasm progression, Pneumonia, Vomiting, Hypercalcaemia, Dysphagia, Diarrhoea, Dehydration, Dyspnoea.

Data from ClinicalTrials.gov NCT02823574 adverse events section.

Sponsor's own description

A study in patients with metastatic or recurrent squamous cell cancer of the head and neck to evaluate the effectiveness of Nivolumab plus Ipilumumab vs. Nivolumab alone (CheckMate 714)

Publications & conference data

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

  1. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.
    Chan TA, Yarchoan M, Jaffee E, Swanton C, et al · · 2019 · cited 2009× · PMID 30395155 · DOI 10.1093/annonc/mdy495
  2. 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
  3. Immunotherapy for Head and Neck Squamous Cell Carcinoma.
    Moskovitz J, Moy J, Ferris RL. · · 2018 · cited 118× · PMID 29502288 · DOI 10.1007/s11912-018-0654-5
  4. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck.
    Argiris A, Harrington KJ, Tahara M, Schulten J, et al · · 2017 · cited 107× · PMID 28536670 · DOI 10.3389/fonc.2017.00072
  5. Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials.
    Kooshkaki O, Derakhshani A, Hosseinkhani N, Torabi M, et al · · 2020 · cited 95× · PMID 32580338 · DOI 10.3390/ijms21124427
  6. Immune Checkpoint Inhibition in Head and Neck Cancer.
    Forster MD, Devlin MJ. · · 2018 · cited 86× · PMID 30211111 · DOI 10.3389/fonc.2018.00310
  7. Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma.
    Wang HC, Chan LP, Cho SF. · · 2019 · cited 68× · PMID 31681613 · DOI 10.3389/fonc.2019.01084
  8. CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.
    Gillison ML, Blumenschein G, Fayette J, Guigay J, et al · · 2018 · cited 67× · PMID 29866947 · DOI 10.1634/theoncologist.2017-0674

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Trials by the same sponsor.

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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/NCT02823574.

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