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

Phase 2

Completed

Conditions: Head and Neck Cancer

Registration Number: NCT02823574

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 425

Inclusion Criteria

Confirmed squamous cell head and neck cancer
Widespread (metastatic) disease, or returned after previous treatment (recurrent)
Tumor sample must be available for analysis of PDL1 (Programmed death-ligand 1) and HPV [Human Papilloma Virus (oropharynx only)]
Performance status ECOG 0-1 (Eastern Cooperative Oncology Group)

Exclusion Criteria

Previous treatment for metastatic or recurrent disease
Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin
Any non-squamous subtype
Active autoimmune disease
Positive test for hepatitis B, C or HIV (Human Immunodeficiency Virus) virus
Previous treatment with checkpoint inhibitor drugs
Active CNS metastases or carcinomatous meningitis

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	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.
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	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.
Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	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).
Overall Survival (OS) - Platinum Refractory Subgroup	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.
Overall Survival (OS)	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.
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup	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).
ORR - Platinum Eligible Subgroup Based on HPV p-16 Status	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.
ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker	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 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.
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	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.
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup	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.
ORR - Platinum Refractory Subgroup Based on HPV p-16 Status	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.
ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker	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 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 Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status	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.
Overall Survival (OS) - Platinum Eligible Subgroup	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.
Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status	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).
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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 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).
Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status	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.
Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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
Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status	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.
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status	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).
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. 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).
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay 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).
Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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
Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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 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).
Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status	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. 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).
Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status	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. 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. 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).
Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay 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).
Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. 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).
ORR - Platinum Refractory Subgroup Based on PD-L1 Expression	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 PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay 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.
Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status	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. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
ORR - Platinum Eligible Subgroup Based on PD-L1 Expression	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 PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay 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.

Trial Locations

Locations (101): University of Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Local Institution - 0034
🇺🇸
Duarte, California, United States
Los Angeles Cancer Network
🇺🇸
Los Angeles, California, United States
Ucla Department Of Medicine
🇺🇸
Los Angeles, California, United States
Local Institution - 0098
🇺🇸
Redondo Beach, California, United States
Local Institution - 0004
🇺🇸
Sacramento, California, United States
Local Institution - 0072
🇺🇸
San Francisco, California, United States
Local Institution - 0097
🇺🇸
San Luis Obispo, California, United States
Central Coast Med Oncology
🇺🇸
Santa Maria, California, United States
Local Institution - 0101
🇺🇸
New Haven, Connecticut, United States
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University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States