Lung Cancer
Conditions
Brief summary
The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).
Interventions
BIOLOGICALNivolumab
Sponsors
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 Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy * Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD) * Measurable disease before start of pre-study nivolumab treatment * Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
Exclusion criteria
* Carcinomatous meningitis * Untreated, symptomatic Central nervous system (CNS) metastases * Symptomatic interstitial lung disease Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate (PFSR) at 6 Months | At 6 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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 Rate (PFSR) at 12 Months | At 12 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | At 12 Months | The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 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. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Overall Survival (OS) Rate at 12 Months | At 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. |
| Overall Survival (OS) Rate up to 60 Months | From randomization to the date of death, Up to 60 Months | The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. |
| Overall Survival Rate by Histology at 12 Months | at 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization. |
| Overall Survival Rate by Response Criteria at 12 Months | 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. 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. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization. |
| Percentage of Participants With an Adverse Events (AEs) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. |
| Progression Free Survival Rate (PFSR) at 24 Months | At 24 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. |
| Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. |
| Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication |
| Percentage of Participants With an Select Adverse Events | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine. |
| Percentage of Participants With an Event of Special Interest (ESI) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD). |
| Percentage of Participants Who Experienced Death | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of Participants who experienced Death due to any cause |
| Number of Participants With Laboratory Test Abnormalities | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined) |
| Percentage of Participants With an Serious Adverse Events (SAEs) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 1. results in death 2. is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) 3. requires inpatient hospitalization or causes prolongation of existing hospitalization 4. results in persistent or significant disability/incapacity 5. is a congenital anomaly/birth defect 6. is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.) |
| Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | At 12 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. |
Countries
Australia, Austria, Canada, France, Germany, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab 480mg Nivolumab 480mg Q4W | 180 |
| Nivolumab 240mg Nivolumab 240mg Q2W | 183 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Other Reason | 2 | 1 |
| Randomization | Participant Withdrew consent | 0 | 2 |
| Treatment Period | Administrative reason by sponsor | 21 | 16 |
| Treatment Period | AE unrelated to Study Drug | 11 | 10 |
| Treatment Period | Death | 7 | 3 |
| Treatment Period | Disease Progression | 82 | 83 |
| Treatment Period | Maximum Clinical Benefit | 5 | 6 |
| Treatment Period | No longer meets study criteria | 2 | 1 |
| Treatment Period | Other Reasons | 22 | 28 |
| Treatment Period | Poor/Non Compliance | 1 | 0 |
| Treatment Period | Requested to Discontinue | 8 | 8 |
| Treatment Period | Study Drug Toxicity | 16 | 19 |
| Treatment Period | Withdrew consent | 3 | 6 |
Baseline characteristics
| Characteristic | Nivolumab 240mg | Total | Nivolumab 480mg |
|---|---|---|---|
| Age, Continuous | 66.5 Years STANDARD_DEVIATION 8.65 | 66.5 Years STANDARD_DEVIATION 8.94 | 66.4 Years STANDARD_DEVIATION 9.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 115 Participants | 233 Participants | 118 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 64 Participants | 123 Participants | 59 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 15 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) White | 168 Participants | 337 Participants | 169 Participants |
| Sex: Female, Male Female | 54 Participants | 103 Participants | 49 Participants |
| Sex: Female, Male Male | 129 Participants | 260 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 88 / 180 | 79 / 183 |
| other Total, other adverse events | 141 / 178 | 168 / 180 |
| serious Total, serious adverse events | 62 / 178 | 71 / 180 |
Outcome results
Primary
Progression Free Survival Rate (PFSR) at 12 Months
The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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.
Time frame: At 12 Months
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) at 12 Months | 0.53 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) at 12 Months | 0.55 Proportion of Participants |
Primary
Progression Free Survival Rate (PFSR) at 6 Months
The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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.
Time frame: At 6 Months
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) at 6 Months | 0.76 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) at 6 Months | 0.79 Proportion of Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypernatremia | 0 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Creatinine | 1 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypocalcemia | 4 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Aspartate Aminotransferase | 1 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypokalemia | 3 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hemoglobin | 0 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypomagnesemia | 3 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphate | 1 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypnatremia | 6 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypercalcemia | 2 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Leukocytes | 1 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hyperkalemia | 4 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Lymphocytes | 22 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Bilirubin, Total | 1 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Neutrophils | 3 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Hypermagnesemia | 4 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Platelet Count | 3 Number of Participants |
| Nivolumab 480mg | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase | 1 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Platelet Count | 1 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase | 1 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphate | 0 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Aspartate Aminotransferase | 2 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Bilirubin, Total | 1 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Creatinine | 2 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hemoglobin | 4 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hyperkalemia | 3 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypermagnesemia | 5 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypernatremia | 0 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypocalcemia | 6 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypokalemia | 6 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypomagnesemia | 2 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypnatremia | 7 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Leukocytes | 3 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Lymphocytes | 21 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Neutrophils | 4 Number of Participants |
| Nivolumab 240mg | Number of Participants With Laboratory Test Abnormalities | Hypercalcemia | 5 Number of Participants |
Secondary
Overall Survival (OS) Rate at 12 Months
The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Time frame: At 12 Months
Population: All Randomized Participants with a response at 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Overall Survival (OS) Rate at 12 Months | 0.851 Proportion of participants |
| Nivolumab 240mg | Overall Survival (OS) Rate at 12 Months | 0.908 Proportion of participants |
Secondary
Overall Survival (OS) Rate up to 60 Months
The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Time frame: From randomization to the date of death, Up to 60 Months
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Overall Survival (OS) Rate up to 60 Months | 12 Months | 0.82 Proportion of participants |
| Nivolumab 480mg | Overall Survival (OS) Rate up to 60 Months | 24 Months | 0.62 Proportion of participants |
| Nivolumab 480mg | Overall Survival (OS) Rate up to 60 Months | 36 Months | 0.49 Proportion of participants |
| Nivolumab 480mg | Overall Survival (OS) Rate up to 60 Months | 48 Months | NA Proportion of participants |
| Nivolumab 240mg | Overall Survival (OS) Rate up to 60 Months | 48 Months | NA Proportion of participants |
| Nivolumab 240mg | Overall Survival (OS) Rate up to 60 Months | 12 Months | 0.88 Proportion of participants |
| Nivolumab 240mg | Overall Survival (OS) Rate up to 60 Months | 36 Months | 0.57 Proportion of participants |
| Nivolumab 240mg | Overall Survival (OS) Rate up to 60 Months | 24 Months | 0.70 Proportion of participants |
Secondary
Overall Survival Rate by Histology at 12 Months
The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization.
Time frame: at 12 Months
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Overall Survival Rate by Histology at 12 Months | Squamous | 0.74 Proportion of participants |
| Nivolumab 480mg | Overall Survival Rate by Histology at 12 Months | Non Squamous | 0.86 Proportion of participants |
| Nivolumab 240mg | Overall Survival Rate by Histology at 12 Months | Squamous | 0.80 Proportion of participants |
| Nivolumab 240mg | Overall Survival Rate by Histology at 12 Months | Non Squamous | 0.92 Proportion of participants |
Secondary
Overall Survival Rate by Response Criteria at 12 Months
The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. 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. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization.
Time frame: 12 Months
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Overall Survival Rate by Response Criteria at 12 Months | CR/PR | 0.90 Proportion of participants |
| Nivolumab 480mg | Overall Survival Rate by Response Criteria at 12 Months | SD | 0.78 Proportion of participants |
| Nivolumab 240mg | Overall Survival Rate by Response Criteria at 12 Months | CR/PR | 0.93 Proportion of participants |
| Nivolumab 240mg | Overall Survival Rate by Response Criteria at 12 Months | SD | 0.85 Proportion of participants |
Secondary
Percentage of Participants Who Experienced Death
Percentage of Participants who experienced Death due to any cause
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Percentage of Participants Who Experienced Death | 49.4 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants Who Experienced Death | 43.9 Percentage of Participants |
Secondary
Percentage of Participants With an Adverse Events (AEs)
Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Adverse Events (AEs) | 91.6 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Adverse Events (AEs) | 97.8 Percentage of Participants |
Secondary
Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC)
Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) | 19.1 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) | 17.8 Percentage of Participants |
Secondary
Percentage of Participants With an Event of Special Interest (ESI)
Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | Pancreatitis | 1.1 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | demyelination | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | encephalitis | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | GBS | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | myasthenic syndrome | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | uveitis | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | myositis | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | myocarditis | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | rhabdomyolysis | 0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Event of Special Interest (ESI) | GVHD | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | myocarditis | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | Pancreatitis | 2.8 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | uveitis | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | demyelination | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | GVHD | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | encephalitis | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | myositis | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | GBS | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | rhabdomyolysis | 0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Event of Special Interest (ESI) | myasthenic syndrome | 0 Percentage of Participants |
Secondary
Percentage of Participants With an Immune Mediated Adverse Events (IMAEs)
Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Hepatitis | 0.0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis | 3.4 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Pneumonitis | 3.4 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Nephritis and Renal Dysfunction | 0.6 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Rash | 7.3 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Hypersensitivity/Infusion Reaction | 0.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Rash | 7.2 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Nephritis and Renal Dysfunction | 0.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis | 5.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Hepatitis | 1.7 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Hypersensitivity/Infusion Reaction | 0.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Pneumonitis | 3.3 Percentage of Participants |
Secondary
Percentage of Participants With an Select Adverse Events
Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine.
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Pulmonary | 6.7 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Skin | 30.9 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Hepatic | 2.2 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Hypersensitivity/Infusion Reaction | 0.0 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Renal | 10.1 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Endocrine | 16.3 Percentage of Participants |
| Nivolumab 480mg | Percentage of Participants With an Select Adverse Events | Gastrointestinal | 18.5 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Endocrine | 18.3 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Gastrointestinal | 25.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Hepatic | 10.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Pulmonary | 5.0 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Renal | 5.6 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Skin | 33.9 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Select Adverse Events | Hypersensitivity/Infusion Reaction | 1.1 Percentage of Participants |
Secondary
Percentage of Participants With an Serious Adverse Events (SAEs)
Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 1. results in death 2. is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) 3. requires inpatient hospitalization or causes prolongation of existing hospitalization 4. results in persistent or significant disability/incapacity 5. is a congenital anomaly/birth defect 6. is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.)
Time frame: Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Percentage of Participants With an Serious Adverse Events (SAEs) | 34.8 Percentage of Participants |
| Nivolumab 240mg | Percentage of Participants With an Serious Adverse Events (SAEs) | 39.4 Percentage of Participants |
Secondary
Progression Free Survival Rate (PFSR) at 24 Months
The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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.
Time frame: At 24 Months
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) at 24 Months | 0.34 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) at 24 Months | 0.35 Proportion of Participants |
Secondary
Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months
The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 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. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: At 12 Months
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | Complete Remission (CR)/Partial Remission (PR) | 0.63 Proportion of Participants |
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | Stable Disease (SD) | 0.47 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | Complete Remission (CR)/Partial Remission (PR) | 0.66 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | Stable Disease (SD) | 0.48 Proportion of Participants |
Secondary
Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months
The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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.
Time frame: At 12 Months
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | Squamous | 0.50 Proportion of Participants |
| Nivolumab 480mg | Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | Non Squamous | 0.54 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | Squamous | 0.42 Proportion of Participants |
| Nivolumab 240mg | Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | Non Squamous | 0.60 Proportion of Participants |