Melanoma
Conditions
Brief summary
The purpose of this study is to determine the rate and frequency of high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-Cytotoxic T Lymphocyte Antigen (CTLA-4) monoclonal antibody, treated with Nivolumab (BMS-936558) at a dose of 3 mg/kg every two weeks.
Interventions
DRUGNivolumab (BMS-936558)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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: * Subjects with histologically confirmed malignant melanoma * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): * PS 0 to 1 * PS 2 * Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines regardless of BRAF mutation status * Subjects must have experienced evaluable Response Evaluation Criteria In Solid Tumors (RECIST 1.1)-defined disease progression * Prior treatment with chemotherapy, interferon (adjuvant setting), Interleukin (IL-2), BRAF/MEK inhibitors for subjects with known BRAF mutations, Mitogen-activated or extracellular signal- regulated protein kinase (MEK) inhibitors for Neuroblastoma Ras Viral (v-ras) oncogene homolog (NRAS) mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed * Patients with CNS metastases are eligible: * if CNS metastases are treated, patients are asymptomatic or neurologically returned to baseline * if they have previously untreated CNS metastases and are asymptomatic * if they have leptomeningeal metastases, are treated and asymptomatic or neurologically returned to baseline with life expectancy \> 3 months * Patients with a known history of Grades 3-4 immune-related adverse reactions during/after anti-CTLA-4 therapy if all toxicities have resolved at least to Grade 1
Exclusion criteria
* Subjects with untreated, active Central Nervous System (CNS) metastases are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Up to 2 years | The number of participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select AEs (pulmonary,gastrointestinal, skin, renal, hepatic, endocrine) were summarized using the all treated analysis set by system organ class and Medical Dictionary for Regulatory (MedDRA) preferred term. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Up to 2 years | The number of Participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), select AEs were summarized using the all treated analysis set by system organ class and MedDRA preferred term. |
| Median Time to Onset (Grades 3-4) of Select Adverse Events | Up to 2 years. | Select AEs were summarized according to their incidence as well as their time to onset. |
| Median Time to Resolution (Grades 3-4) of Select Adverse Events | Up to 2 years | Select AEs were summarized according to their incidence as well as their time to resolution |
| Overall Survival | Up to 4 years | The time from first dosing date to the date of death. |
Countries
Austria, Belgium, Czechia, Finland, Germany, Greece, Hungary, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, Russia, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Pre-assignment details
1009 participants were enrolled into the study , 1008 wrere treated, 1 participants was not treated due to withdrew consent
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab 3mg/kg Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks | 1,008 |
| Total | 1,008 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Nivolumab 3mg/kg |
|---|---|
| Age, Continuous | 60.1 Years STANDARD_DEVIATION 13.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 972 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) White | 987 Participants |
| Sex: Female, Male Female | 451 Participants |
| Sex: Female, Male Male | 557 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 527 / 1,008 |
| other Total, other adverse events | 857 / 1,008 |
| serious Total, serious adverse events | 593 / 1,008 |
Outcome results
Primary
the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events.
The number of participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select AEs (pulmonary,gastrointestinal, skin, renal, hepatic, endocrine) were summarized using the all treated analysis set by system organ class and Medical Dictionary for Regulatory (MedDRA) preferred term.
Time frame: Up to 2 years
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Gastrointestinal Adverse events (Grade 3-4) | 16 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Gastrointestinal adverse events (Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Hepatic adverse events (Grade 3-4) | 30 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Hepatic adverse events (Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Pulmonary adverse events(Grade 3-4) | 6 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Pulmonary adverse events(Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Renal adverse events (Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Skin adverse events ( Grade 3-4) | 13 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Skin adverse events ( Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Hypersensitivity adverse event( Grade 3-4) | 1 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Hypersensitivity adverse event( Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Endocrine adverse events(Grade 3-4) | 18 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Endocrine adverse events(Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. | Renal adverse events (Grade 3-4) | 4 Number of Participants |
Secondary
Median Time to Onset (Grades 3-4) of Select Adverse Events
Select AEs were summarized according to their incidence as well as their time to onset.
Time frame: Up to 2 years.
Population: All Treated Participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Endocrine Adverse Events | 12 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Gastrointestinal Adverse Events | 23.50 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Skin Adverse Events | 34.36 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Hypersensitivity/infusion reaction Adverse Events | 29.57 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Hepatic Adverse Events | 10.14 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Pulmonary Adverse Events | 14.86 Weeks |
| Nivolumab 3mg/kg | Median Time to Onset (Grades 3-4) of Select Adverse Events | Renal Adverse Events | 11.71 Weeks |
Secondary
Median Time to Resolution (Grades 3-4) of Select Adverse Events
Select AEs were summarized according to their incidence as well as their time to resolution
Time frame: Up to 2 years
Population: All Treated Participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Endocrine Adverse Events | 2.43 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Gastrointestinal Adverse Events | 3.71 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Hepatic Adverse Events | 9.43 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Pulmonary Adverse Events | 2.57 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Renal Adverse Events | 1.93 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Skin Adverse Events | 5.07 Weeks |
| Nivolumab 3mg/kg | Median Time to Resolution (Grades 3-4) of Select Adverse Events | Hypersensitivity/infusion reaction Adverse Events | 0.29 Weeks |
Secondary
Overall Survival
The time from first dosing date to the date of death.
Time frame: Up to 4 years
Population: All Treated Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 3mg/kg | Overall Survival | 21.2 Months |
Secondary
The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events
The number of Participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), select AEs were summarized using the all treated analysis set by system organ class and MedDRA preferred term.
Time frame: Up to 2 years
Population: All treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Gastrointestinal Adverse events (Grade 3-4) | 24 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Renal adverse events (Grade 3-4) | 12 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Gastrointestinal adverse events (Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Hepatic adverse events (Grade 3-4) | 52 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Hepatic adverse events (Grade 5) | 1 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Pulmonary adverse events(Grade 3-4) | 7 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Pulmonary adverse events(Grade 5) | 1 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Renal adverse events (Grade 5) | 1 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Skin adverse events ( Grade 3-4) | 19 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Skin adverse events ( Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Hypersensitivity adverse event( Grade 3-4) | 2 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Hypersensitivity adverse event( Grade 5) | 0 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Endocrine adverse events(Grade 3-4) | 24 Number of Participants |
| Nivolumab 3mg/kg | The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events | Endocrine adverse events(Grade 5) | 0 Number of Participants |