Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief summary
The purpose of this study is to find out whether Nivolumab will significantly improve overall survival as compared to therapy of investigator's choice in patients with recurrent or metastatic head and neck carcinoma.
Interventions
DRUGMethotrexate
DRUGDocetaxel
DRUGNivolumab
DRUGCetuximab
Sponsors
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Men and women ≥ 18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 * Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy) * Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting * Measurable disease by Computed tomography (CT) or Magnetic resonance imaging (MRI) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria
Exclusion criteria
* Active brain metastases or leptomeningeal metastases are not allowed * Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg: mucosal melanoma) are not allowed * Subjects with active, known or suspected autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of randomization to date of death (Up to approximately 18 months) | OS 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. Median OS time was calculated using Kaplan-Meier (KM) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-Assessed Progression-Free Survival (PFS) | From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months) | PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who: * Die without a reported progression were considered to have progressed on the date of their death. * Did not progress or die were censored on the date of their last evaluable tumor assessment. * Without any on study tumor assessments and did not die were censored on their date of randomization. * Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy. |
| Investigator-Assessed Objective Response Rate (ORR) | From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months) | ORR was defined as the percentage of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. |
Countries
Argentina, Brazil, Canada, France, Germany, Hong Kong, Italy, Japan, Netherlands, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab 3mg/kg Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression. | 240 |
| Investigators Choice Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligrams per square meter (mg/m\^2) for the first dose followed that a doses of 250 mg/m\^2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m\^2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m\^2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice | 121 |
| Total | 361 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-Treatment | Disease Progression | 1 | 0 |
| Pre-Treatment | Participant no longer meets study criteria | 2 | 2 |
| Pre-Treatment | Participant request to discontinue study treatment | 1 | 2 |
| Pre-Treatment | Participant withdrew consent | 0 | 6 |
| Treatment | Adverse event unrelated to study drug | 19 | 3 |
| Treatment | Disease Progression | 185 | 87 |
| Treatment | Lost to Follow-up | 1 | 0 |
| Treatment | Maximum Clinical Benefit | 1 | 3 |
| Treatment | Other reasons | 1 | 0 |
| Treatment | Participant no longer meets study criteria | 1 | 0 |
| Treatment | Participant request to discontinue study treatment | 8 | 6 |
| Treatment | Participant withdrew consent | 5 | 1 |
| Treatment | Poor/Non-compliance | 0 | 1 |
| Treatment | Study Drug Toxicity | 14 | 10 |
Baseline characteristics
| Characteristic | Nivolumab 3mg/kg | Investigators Choice | Total |
|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 10.15 | 59.4 years STANDARD_DEVIATION 11 | 59.1 years STANDARD_DEVIATION 10.43 |
| Age, Customized >=65 and <75 years | 56 Participants | 39 Participants | 95 Participants |
| Age, Customized < 65 years | 172 Participants | 76 Participants | 248 Participants |
| Age, Customized >=75 years | 12 Participants | 6 Participants | 18 Participants |
| Race/Ethnicity, Customized Asian | 29 Participants | 14 Participants | 43 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 3 Participants | 13 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 9 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 132 Participants | 60 Participants | 192 Participants |
| Race/Ethnicity, Customized Not Reported | 99 Participants | 57 Participants | 156 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 196 Participants | 104 Participants | 300 Participants |
| Sex: Female, Male Female | 43 Participants | 18 Participants | 61 Participants |
| Sex: Female, Male Male | 197 Participants | 103 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 220 / 240 | 119 / 121 |
| other Total, other adverse events | 210 / 236 | 108 / 111 |
| serious Total, serious adverse events | 165 / 236 | 87 / 111 |
Outcome results
Primary
Overall Survival (OS)
OS 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. Median OS time was calculated using Kaplan-Meier (KM) method.
Time frame: From date of randomization to date of death (Up to approximately 18 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3mg/kg | Overall Survival (OS) | 7.49 Months |
| Investigators Choice | Overall Survival (OS) | 5.06 Months |
Comparison: Stratified Cox proportional hazard model. HR = Nivolumab over investigator's choice therapy (Cetuximab, Methotrexate, or Docetaxel)p-value: 0.010195% CI: [0.53, 0.92]Log Rank
Secondary
Investigator-Assessed Objective Response Rate (ORR)
ORR was defined as the percentage of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Time frame: From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 3mg/kg | Investigator-Assessed Objective Response Rate (ORR) | 13.3 Percentage of Participants |
| Investigators Choice | Investigator-Assessed Objective Response Rate (ORR) | 5.8 Percentage of Participants |
95% CI: [1.5, 13.6]
95% CI: [1.07, 5.82]
Secondary
Investigator-Assessed Progression-Free Survival (PFS)
PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who: * Die without a reported progression were considered to have progressed on the date of their death. * Did not progress or die were censored on the date of their last evaluable tumor assessment. * Without any on study tumor assessments and did not die were censored on their date of randomization. * Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.
Time frame: From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3mg/kg | Investigator-Assessed Progression-Free Survival (PFS) | 2.04 Months |
| Investigators Choice | Investigator-Assessed Progression-Free Survival (PFS) | 2.33 Months |
95% CI: [0.68, 1.1]
Post Hoc
Overall Survival (OS) - Extended Collection
OS 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. Median OS time was calculated using Kaplan-Meier (KM) method. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 10-Sep-2021)
Time frame: From date of randomization to date of death (Up to approximately 87 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3mg/kg | Overall Survival (OS) - Extended Collection | 7.72 Months |
| Investigators Choice | Overall Survival (OS) - Extended Collection | 5.06 Months |
95% CI: [0.54, 0.85]