Melanoma
Conditions
Keywords
ipilimumab, previously treated
Brief summary
The purpose of this study was to evaluate the continued use of ipilimumab in patients who had reinduction at the time of disease progression or to continue maintenance treatment. In addition, this study will continue to follow patients who have taken ipilimumab, but who are not eligible for maintenance or reinduction therapy.
Interventions
DRUGIpilimumab
Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_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 Key Inclusion Criteria * Diagnosis of advanced melanoma * Prior treatment in a prespecified prior/parent ipilimumab study * Men and women 18 years of age and older First Reinduction: * No unacceptable toxicity (except select reversible immune-related adverse events) requiring ipilimumab discontinuation * Had experienced documented progressive disease after expanded clinical benefit Extended Maintenance * Received ipilimumab at any dose in a parent study * Achieved expanded clinical benefit at the time of entry to current study Follow-up: * Received ipilimumab at any dose in a closing parent study * Deemed ineligible for reinduction or extended maintenance treatment or refused treatment as reinduction or extended maintenance at the time of screening in the current study, but consented to follow-up Key
Exclusion criteria
* Prior treatment with a CD137 agonist or a cytotoxic T-lymphocyte antigen 4 inhibitor or agonist, other than ipilimumab * Primary ocular or mucosal melanoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Continuously from first dose to 70 days after last dose of study drug. For deaths, Day 1 of enrollment to 70 days after last dose of study drug. | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. An SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related is defined as having certain, probable, possible, or missing relationship to study drug. An IrAE is an AE characterized by a potential association with inflammation and considered by the investigator to be drug related. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From first dose of study drug in parent study to death or date of last censoring. | OS was computed for all patients who entered this study and is defined as the time between the first dose of study therapy and death. If a patient has not died, OS was censored at the time of last contact. |
| Percentage of Participants Surviving at 1, 1.5, and 2 Years | From first dose of study drug in parent study to up to 2 years after reinduction | Survival rate was defined as the time from first dose of study drug to 1, 1.5, and 2 years. |
| Number of Participants With On-study Immune-related Adverse Events (irAEs) | From first dose of study drug during reinduction to the earliest of 70 days after last dose or day before second reinduction first dose date | irAEs were defined as adverse events characterized by a potential association with inflammation and considered by the investigator as drug related. These prespecified terms were grouped into the following organ-specific subcategories: gastrointestinal, hepatic, skin, endocrine, neurologic, and other (includes blood, eye, immune system, investigations, infections, renal, and respiratory systems). Patients may have 1 or more events. |
| Progression-free Survival (PFS) | From day of first reinduction in current study to date of progression or death, whichever occurred first. | PFS was defined as the time between the date of the baseline tumor assessment in this study and the date of progression or death, whichever occurred first. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Israel, Italy, Norway, Poland, Russia, South Africa, Spain, Ukraine, United States
Participant flow
Pre-assignment details
Of 248 enrolled, 6 failed screening; 28 from study CA184-004 (NCT00261365), 42 from CA184-007 (NCT00135408), 67 from CA184-008 (NCT00289627), and 103 from CA184-022 (NCT00289640) entered CA184-025 (NCT00162123). Of enrollees, 2 from study MDX010-08 (NCT00050102) and 6 from MDX010-15 (NCT00729950) entered maintenance as Tumor Assessment Only.
Participants by arm
| Arm | Count |
|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg Participants who initially received ipilimumab, 10 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | 53 |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg Participants who initially received ipilimumab, 3 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | 34 |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg Participants who initially received ipilimumab, 0.3 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | 24 |
| First Reinduction: Ipilimumab, Other Dosage Participants who received a dose other than 10, 3, or 0.3 mg/kg ipilimumab in parent study received a first reinduction of either 3 or 10 mg/kg in current study. | 11 |
| Extended Maintenance: Ipilimumab, 10 mg/kg Participants who received ipilimumab, 10 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (10 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | 45 |
| Extended Maintenance: Ipilimumab, 3 mg/kg Participants who received ipilimumab, 3 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (3 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | 13 |
| Extended Maintenance: Ipilimumab, 0.3 mg/kg Participants who received ipilimumab, 0.3 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (0.3 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | 4 |
| Follow-up Participants did not receive any additional study treatment in current study but continued follow-up for the collection of survival data. | 58 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 2 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 3 | 3 | 1 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Deterioration without progression | 2 | 2 | 3 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Disease progression | 27 | 19 | 10 | 4 | 8 | 3 | 1 | 0 |
| Overall Study | Follow-up only (not treated or assessed) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 57 |
| Overall Study | Not specified (after start of treatment) | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 |
| Overall Study | Not specified (before treatment) | 2 | 0 | 0 | 0 | 12 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Study drug toxicity | 6 | 1 | 5 | 0 | 4 | 1 | 1 | 0 |
| Overall Study | Tumor assessment only (not treated) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 | 1 | 1 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | First Reinduction: Ipilimumab, 3 to 10 mg/kg | Total | Follow-up | Extended Maintenance: Ipilimumab, 0.3 mg/kg | Extended Maintenance: Ipilimumab, 3 mg/kg | Extended Maintenance: Ipilimumab, 10 mg/kg | First Reinduction: Ipilimumab, 10 to 10 mg/kg | First Reinduction: Ipilimumab, Other Dosage | First Reinduction: Ipilimumab, 0.3 to 10 mg/kg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 9.9 | 57.7 Years STANDARD_DEVIATION 12.55 | 56.3 Years STANDARD_DEVIATION 12.96 | 65.5 Years STANDARD_DEVIATION 4.8 | 59.0 Years STANDARD_DEVIATION 16.65 | 60.5 Years STANDARD_DEVIATION 12.42 | 55.4 Years STANDARD_DEVIATION 11.7 | 57.8 Years STANDARD_DEVIATION 13.7 | 56.0 Years STANDARD_DEVIATION 15.3 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 22 Units on a scale | 162 Units on a scale | 29 Units on a scale | 3 Units on a scale | 12 Units on a scale | 40 Units on a scale | 37 Units on a scale | 9 Units on a scale | 10 Units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 11 Units on a scale | 59 Units on a scale | 10 Units on a scale | 1 Units on a scale | 1 Units on a scale | 5 Units on a scale | 16 Units on a scale | 2 Units on a scale | 13 Units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 1 Units on a scale | 3 Units on a scale | 1 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 1 Units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 | 0 Units on a scale | 1 Units on a scale | 1 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Not reported | 0 Units on a scale | 17 Units on a scale | 17 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale | 0 Units on a scale |
| Race/Ethnicity, Customized American Indian/Alaska native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other: Brazilian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 236 Participants | 55 Participants | 4 Participants | 13 Participants | 45 Participants | 51 Participants | 10 Participants | 24 Participants |
| Sex: Female, Male Female | 11 Participants | 85 Participants | 22 Participants | 1 Participants | 5 Participants | 20 Participants | 21 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 23 Participants | 157 Participants | 36 Participants | 3 Participants | 8 Participants | 25 Participants | 32 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 53 | 32 / 34 | 21 / 24 | 9 / 11 | 28 / 33 | 11 / 12 | 3 / 4 | 34 / 58 |
| serious Total, serious adverse events | 23 / 53 | 19 / 34 | 14 / 24 | 7 / 11 | 12 / 33 | 3 / 12 | 2 / 4 | 20 / 58 |
Outcome results
Primary
Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. An SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related is defined as having certain, probable, possible, or missing relationship to study drug. An IrAE is an AE characterized by a potential association with inflammation and considered by the investigator to be drug related. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time frame: Continuously from first dose to 70 days after last dose of study drug. For deaths, Day 1 of enrollment to 70 days after last dose of study drug.
Population: All participants who received study drug as reinduction from 0.3, 3, or 10 mg/kg doses in parent study and 10 mg/kg in current study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 3 or 4 | 18 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Any grade | 30 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Any Grade | 51 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 3 or 4 | 7 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 5 (Fatal) | 4 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Deaths | 36 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Any grade | 23 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Any grade | 42 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 3 or 4 | 13 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 5 (Fatal) | 1 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 3 or 4 | 9 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 3 or 4 | 9 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Any grade | 13 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 5 (Fatal) | 4 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 3 or 4 | 3 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Any grade | 6 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Any grade | 23 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 5 (Fatal) | 7 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Any grade | 28 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 3 or 4 | 2 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Deaths | 27 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Any Grade | 33 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 3 or 4 | 10 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 5 (Fatal) | 7 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 3 or 4 | 3 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 5 (Fatal) | 2 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Any grade | 19 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 3 or 4 | 8 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 3 or 4 | 5 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 5 (Fatal) | 8 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 3 or 4 | 9 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Any grade | 8 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Grade 3 or 4 | 10 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Any grade | 14 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 3 or 4 | 6 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Any grade | 21 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 3 or 4 | 6 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Deaths | 19 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | irAEs: Any grade | 18 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs leading to discontinuation: Grade 5 (Fatal) | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | AEs: Any Grade | 24 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | Drug-related AEs: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | SAEs: Grade 5 (Fatal) | 8 Participants |
Secondary
Number of Participants With On-study Immune-related Adverse Events (irAEs)
irAEs were defined as adverse events characterized by a potential association with inflammation and considered by the investigator as drug related. These prespecified terms were grouped into the following organ-specific subcategories: gastrointestinal, hepatic, skin, endocrine, neurologic, and other (includes blood, eye, immune system, investigations, infections, renal, and respiratory systems). Patients may have 1 or more events.
Time frame: From first dose of study drug during reinduction to the earliest of 70 days after last dose or day before second reinduction first dose date
Population: All participants who received study drug as reinduction from 0.3, 3, or 10 mg/kg doses in parent study 10 mg/kg current study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Any grade | 18 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Any grade | 3 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Any grade | 2 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Grade 3 or 4 | 2 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Any grade | 3 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Any grade | 30 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Any grade | 1 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Any grade | 11 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Grade 3 or 4 | 2 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Grade 3 or 4 | 2 Participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 3 or 4 | 7 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 3 or 4 | 2 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Any grade | 23 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Any grade | 7 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Any grade | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Any grade | 2 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Any grade | 18 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Any grade | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Any grade | 3 Participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Any grade | 10 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Any grade | 14 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Any grade | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Skin irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 5 (Fatal) | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Other irAE: Grade 3 or 4 | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Any grade | 0 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Grade 3 or 4 | 6 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Any grade | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Hepatic irAE: Any grade | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Any irAE: Any grade | 18 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Endocrine irAE: Grade 3 or 4 | 1 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Gastrointestinal irAE: Grade 3 or 4 | 3 Participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Number of Participants With On-study Immune-related Adverse Events (irAEs) | Neurologic irAE: Grade 3 or 4 | 0 Participants |
Secondary
Overall Survival (OS)
OS was computed for all patients who entered this study and is defined as the time between the first dose of study therapy and death. If a patient has not died, OS was censored at the time of last contact.
Time frame: From first dose of study drug in parent study to death or date of last censoring.
Population: All participants who received study drug as reinduction from 0.3, 3, or 10 mg/kg doses in parent study and 10 mg/kg in current study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Overall Survival (OS) | 30.8 Months |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Overall Survival (OS) | 18.7 Months |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Overall Survival (OS) | 15.2 Months |
Secondary
Percentage of Participants Surviving at 1, 1.5, and 2 Years
Survival rate was defined as the time from first dose of study drug to 1, 1.5, and 2 years.
Time frame: From first dose of study drug in parent study to up to 2 years after reinduction
Population: All participants who received study drug as reinduction or extended maintenance from 0.3, 3, or 10 mg/kg doses in parent study and 10 mg/kg in current study and those patients who were followed-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 71.3 Percentage of participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 63.6 Percentage of participants |
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 80.9 Percentage of participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 50.0 Percentage of participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 55.9 Percentage of participants |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 38.2 Percentage of participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 35.0 Percentage of participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 65.6 Percentage of participants |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 30.6 Percentage of participants |
| Extended Maintenance: Ipilimumab, 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 100 Percentage of participants |
| Extended Maintenance: Ipilimumab, 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 100 Percentage of participants |
| Extended Maintenance: Ipilimumab, 10 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 91.0 Percentage of participants |
| Extended Maintenance: Ipilimumab, 3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 84.6 Percentage of participants |
| Extended Maintenance: Ipilimumab, 3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 100 Percentage of participants |
| Extended Maintenance: Ipilimumab, 3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 84.6 Percentage of participants |
| Extended Maintenance: Ipilimumab, 0.3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 75.0 Percentage of participants |
| Extended Maintenance: Ipilimumab, 0.3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 75.0 Percentage of participants |
| Extended Maintenance: Ipilimumab, 0.3 mg/kg | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 75.0 Percentage of participants |
| Follow-up | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 2 years | 64.9 Percentage of participants |
| Follow-up | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1.5 years | 79.0 Percentage of participants |
| Follow-up | Percentage of Participants Surviving at 1, 1.5, and 2 Years | 1 year | 87.8 Percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time between the date of the baseline tumor assessment in this study and the date of progression or death, whichever occurred first.
Time frame: From day of first reinduction in current study to date of progression or death, whichever occurred first.
Population: All participants who received study drug as reinduction from 0.3, 3, or 10 mg/kg doses in parent study and 10 mg/kg in current study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Reinduction: Ipilimumab, 10 to 10 mg/kg | Progression-free Survival (PFS) | 3.4 Months |
| First Reinduction: Ipilimumab, 3 to 10 mg/kg | Progression-free Survival (PFS) | 2.6 Months |
| First Reinduction: Ipilimumab, 0.3 to 10 mg/kg | Progression-free Survival (PFS) | 2.6 Months |