Melanoma
Conditions
Brief summary
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
Interventions
DRUGIpilimumab
Specified dose on specified days
DRUGNivolumab
Specified dose on specified days
Specified dose on specified days
OTHERPlacebo matching Nivolumab
Specified dose on specified days
Sponsors
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 15 years of age Except: where local regulations and/or institutional policies do not allow for subjects \< 18 years of age (pediatric population) to participate. For those sites, the eligible subject population is ≥ 18 years of age * Completely removed melanoma by surgery performed within 12 weeks of randomization * Stage IIIb/C or Stage IV before complete resection * No previous anti-cancer treatment
Exclusion criteria
* Ocular or uveal melanoma * History of carcinomatosis meningitis * History of auto-immune disease * Treatment directed against the resected melanoma that is administrated after the surgery Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free Survival (RFS) | up to 36 months | RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 106.6 months | OS is defined as as the time between the date of randomization and the date of death. |
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | reported between the first dose and 30 days after last dose of study therapy | The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events |
| the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths | reported between first dose and 30 to 100 days after last dose of study therapy | the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of Deaths |
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | reported between first dose and 30 days after last dose of study therapy | the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events |
| Recurrence-free Survival by PD-L1 Expression | up to 106.6 months | Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression) |
| Health Related Quality of Life (HRQoL) Evaluation | up to 36 months | HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 global health status/QoL composite scale and in remaining EORTC QLQ-C30 scales in all randomized participants. EORTC QLQ-C30 is the most commonly used QoL instrument in melanoma clinical studies, is a 30-item instrument that has gained wide acceptance in oncology clinical studies and comprises 5 functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Except for the overall health status and global quality of life items, responses for all items are 4 point categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health status/quality of life responses are 7-point Likert scales for which higher score reflects higher health status/quality of life for the 7-point Likert scale. |
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | reported after first dose and within 30 days of last dose of the study therapy | The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Czechia, Finland, France, Greece, Hungary, Ireland, Italy, Japan, Netherlands, Norway, Poland, Romania, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
906 participants randomized and 905 treated. Reason for not treated: 1 participant withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab 3 mg/kg Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24 | 453 |
| Ipilimumab 10 mg/kg Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks | 453 |
| Total | 906 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-Treatment Period | Participant withdrew consent | 1 | 0 |
| Treatment Period | Adverse Event (AE) unrelated to study drug | 5 | 5 |
| Treatment Period | Disease progression | 121 | 100 |
| Treatment Period | Other reasons | 3 | 3 |
| Treatment Period | Participant no longer meets study criteria | 0 | 1 |
| Treatment Period | Participant request to stop treatment | 5 | 9 |
| Treatment Period | Participant withdrew consent | 2 | 3 |
| Treatment Period | Poor/non-compliance | 0 | 1 |
| Treatment Period | Study drug toxicity | 41 | 208 |
Baseline characteristics
| Characteristic | Total | Nivolumab 3 mg/kg | Ipilimumab 10 mg/kg |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 13.42 | 54.4 years STANDARD_DEVIATION 13.34 | 53.6 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 423 Participants | 215 Participants | 208 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 469 Participants | 232 Participants | 237 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 43 Participants | 25 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 859 Participants | 425 Participants | 434 Participants |
| Sex: Female, Male Female | 379 Participants | 195 Participants | 184 Participants |
| Sex: Female, Male Male | 527 Participants | 258 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 128 / 452 | 142 / 453 |
| other Total, other adverse events | 421 / 452 | 438 / 453 |
| serious Total, serious adverse events | 106 / 452 | 215 / 453 |
Outcome results
Primary
Recurrence-free Survival (RFS)
RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.
Time frame: up to 36 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3 mg/kg | Recurrence-free Survival (RFS) | 52.37 Months |
| Ipilimumab 10 mg/kg | Recurrence-free Survival (RFS) | 24.08 Months |
p-value: 0.000395% CI: [0.6, 0.86]Log Rank
Secondary
Health Related Quality of Life (HRQoL) Evaluation
HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 global health status/QoL composite scale and in remaining EORTC QLQ-C30 scales in all randomized participants. EORTC QLQ-C30 is the most commonly used QoL instrument in melanoma clinical studies, is a 30-item instrument that has gained wide acceptance in oncology clinical studies and comprises 5 functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Except for the overall health status and global quality of life items, responses for all items are 4 point categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health status/quality of life responses are 7-point Likert scales for which higher score reflects higher health status/quality of life for the 7-point Likert scale.
Time frame: up to 36 months
Population: All randomized Participants with values from the second follow-up visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Appetite loss | 4.07 Scores on a scale | Standard Deviation 22.66 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Global health status | -5.81 Scores on a scale | Standard Deviation 20.046 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Emotional functioning | 0.18 Scores on a scale | Standard Deviation 20.282 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Fatigue | 6.45 Scores on a scale | Standard Deviation 21.605 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Nausea and vomiting | 2.23 Scores on a scale | Standard Deviation 12.622 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Physical functioning | -2.04 Scores on a scale | Standard Deviation 15.134 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Pain | 1.66 Scores on a scale | Standard Deviation 23.314 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Cognitive functioning | -3.74 Scores on a scale | Standard Deviation 18.364 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Dyspnea | 7.32 Scores on a scale | Standard Deviation 22.741 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Constipation | 1.11 Scores on a scale | Standard Deviation 17.904 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Insomnia | 1.82 Scores on a scale | Standard Deviation 28.692 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Diarrhea | 1.31 Scores on a scale | Standard Deviation 20.831 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Role functioning | -2.43 Scores on a scale | Standard Deviation 25.219 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Financial difficulties | -1.41 Scores on a scale | Standard Deviation 23.348 |
| Nivolumab 3 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Social functioning | -0.51 Scores on a scale | Standard Deviation 22.085 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Financial difficulties | 0.54 Scores on a scale | Standard Deviation 20.282 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Dyspnea | 5.45 Scores on a scale | Standard Deviation 20.364 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Insomnia | 3.05 Scores on a scale | Standard Deviation 28.785 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Physical functioning | -4.88 Scores on a scale | Standard Deviation 15.713 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Role functioning | -3.85 Scores on a scale | Standard Deviation 29.951 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Emotional functioning | 1.43 Scores on a scale | Standard Deviation 17.911 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Cognitive functioning | -4.67 Scores on a scale | Standard Deviation 16.664 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Appetite loss | 2.61 Scores on a scale | Standard Deviation 19.257 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Social functioning | -3.53 Scores on a scale | Standard Deviation 26.391 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Global health status | -7.00 Scores on a scale | Standard Deviation 23.109 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Nausea and vomiting | 1.90 Scores on a scale | Standard Deviation 11.473 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Pain | 4.38 Scores on a scale | Standard Deviation 23.641 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Constipation | 0.33 Scores on a scale | Standard Deviation 18.373 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Diarrhea | 3.38 Scores on a scale | Standard Deviation 21.242 |
| Ipilimumab 10 mg/kg | Health Related Quality of Life (HRQoL) Evaluation | Fatigue | 9.05 Scores on a scale | Standard Deviation 23.475 |
Secondary
Overall Survival (OS)
OS is defined as as the time between the date of randomization and the date of death.
Time frame: up to 106.6 months
Population: All randomized Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3 mg/kg | Overall Survival (OS) | NA Months |
| Ipilimumab 10 mg/kg | Overall Survival (OS) | NA Months |
95.03% CI: [0.69, 1.11]Log Rank
Secondary
Recurrence-free Survival by PD-L1 Expression
Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression)
Time frame: up to 106.6 months
Population: All randomized Participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nivolumab 3 mg/kg | Recurrence-free Survival by PD-L1 Expression | Participants with >= 5% PD-L1 Expression, | 70.41 Months |
| Nivolumab 3 mg/kg | Recurrence-free Survival by PD-L1 Expression | Participants with < 5% PD-L1 Expression, | 38.677 Months |
| Ipilimumab 10 mg/kg | Recurrence-free Survival by PD-L1 Expression | Participants with >= 5% PD-L1 Expression, | 54.67 Months |
| Ipilimumab 10 mg/kg | Recurrence-free Survival by PD-L1 Expression | Participants with < 5% PD-L1 Expression, | 16.56 Months |
Secondary
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events
Time frame: reported between first dose and 30 days after last dose of study therapy
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | Grade 3-4 | 116 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | Any grade | 440 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | Grade 3-4 | 251 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | Any grade | 446 Participants |
Secondary
the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths
the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of Deaths
Time frame: reported between first dose and 30 to 100 days after last dose of study therapy
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 3 mg/kg | the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths | 128 Participants |
| Ipilimumab 10 mg/kg | the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths | 142 Participants |
Secondary
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities
The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities.
Time frame: reported after first dose and within 30 days of last dose of the study therapy
Population: Participants with a CTC graded Laboratory Result for the given parameter from both Baseline and On-treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Absolute Neutrophil count (Grade3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Leukocytes (grade1-4) | 62 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypercalcemia ( grade1-4) | 14 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Heamoglobin (grade1-4) | 114 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Heamoglobin (Grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Platelet count (grade1-4) | 27 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Leukocytes (grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Lymphocytes (grade1-4) | 118 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Lymphocytes (grade 3-4) | 2 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Absolute Neutrophil count (Grade1-4) | 56 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Platelet count ( grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Phosphatase (grade1-4) | 35 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Phosphatase (Grade3-4) | 1 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Aspartate Aminotransferase (grade 1-4) | 105 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Aspartate Aminotransferase(grade 3-4) | 6 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Aminotransferase (grade 1-4) | 113 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Aminotransferase(grade 3-4) | 8 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Bilirubin (grade 1-4) | 33 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Bilirubin (grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Creatinine ( grade1-4) | 55 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Creatinine (grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Amylase ( grade1-4) | 68 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Amylase (grade 3-4) | 13 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Lipase ( grade1-4) | 109 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Lipase (grade 3-4) | 31 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypernatremia ( grade1-4) | 35 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypernatremia (grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyponatremia ( grade1-4) | 72 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyponatremia (grade 3-4) | 5 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyperkalemia ( grade1-4) | 55 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyperkalemia (grade 3-4) | 1 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypokalemia ( grade1-4) | 37 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypokalemia(grade 3-4) | 5 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypercalcemia(grade 3-4) | 0 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypocalcemia ( grade1-4) | 46 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypocalcemia(grade 3-4) | 3 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypermagnesemia ( grade1-4) | 20 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypermagnesemia(grade 3-4) | 2 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypomagnesemia ( grade1-4) | 39 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypomagnesemia(grade 3-4) | 1 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypermagnesemia(grade 3-4) | 1 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Platelet count ( grade 3-4) | 1 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Creatinine (grade 3-4) | 0 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Leukocytes (grade1-4) | 12 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyperkalemia (grade 3-4) | 2 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypercalcemia ( grade1-4) | 18 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Amylase ( grade1-4) | 52 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Heamoglobin (grade1-4) | 148 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypocalcemia(grade 3-4) | 2 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Heamoglobin (Grade 3-4) | 2 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Amylase (grade 3-4) | 12 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Platelet count (grade1-4) | 25 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypokalemia ( grade1-4) | 45 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Leukocytes (grade 3-4) | 1 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Lipase ( grade1-4) | 100 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Lymphocytes (grade1-4) | 54 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypomagnesemia(grade 3-4) | 0 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Lymphocytes (grade 3-4) | 4 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Lipase (grade 3-4) | 38 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Absolute Neutrophil count (Grade1-4) | 26 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypokalemia(grade 3-4) | 9 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Absolute Neutrophil count (Grade3-4) | 2 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypernatremia ( grade1-4) | 20 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Phosphatase (grade1-4) | 69 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypermagnesemia ( grade1-4) | 7 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Phosphatase (Grade3-4) | 3 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypernatremia (grade 3-4) | 0 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Aspartate Aminotransferase (grade 1-4) | 144 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypercalcemia(grade 3-4) | 0 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Aspartate Aminotransferase(grade 3-4) | 39 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyponatremia ( grade1-4) | 96 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Aminotransferase (grade 1-4) | 176 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypomagnesemia ( grade1-4) | 32 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Alkaline Aminotransferase(grade 3-4) | 52 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyponatremia (grade 3-4) | 14 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Bilirubin (grade 1-4) | 43 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hypocalcemia ( grade1-4) | 73 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Total Bilirubin (grade 3-4) | 5 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Hyperkalemia ( grade1-4) | 39 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | Creatinine ( grade1-4) | 56 Participants |
Secondary
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events
The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events
Time frame: reported between the first dose and 30 days after last dose of study therapy
Population: all treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | Grade 3-4 | 48 Participants |
| Nivolumab 3 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | Any grade | 80 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | Grade 3-4 | 145 Participants |
| Ipilimumab 10 mg/kg | The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | Any grade | 184 Participants |
Post Hoc
Recurrence-free Survival (RFS)
RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.
Time frame: up to 114 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3 mg/kg | Recurrence-free Survival (RFS) | 61.14 Months |
| Ipilimumab 10 mg/kg | Recurrence-free Survival (RFS) | 24.15 Months |
95% CI: [0.63, 0.9]Log Rank