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MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT00094653
Recruitment Status : Completed
First Posted : October 22, 2004
Results First Posted : June 23, 2011
Last Update Posted : July 11, 2011
Sponsor:
Information provided by:
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Melanoma
Metastases
Interventions Drug: MDX-010 (anti-CTLA4) monoclonal antibody
Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
Enrollment 1783
Recruitment Details  
Pre-assignment Details Of the 1783 participants who enrolled and were screened for study participation, a total of 676 subjects were randomized.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Period Title: Overall Study
Started 403 137 136
Treated 381 131 131
Completed 82 31 10
Not Completed 321 106 126
Reason Not Completed
Death             306             100             119
Subject Withdrew Consent             10             2             3
Not specified             2             2             2
Lost to Follow-up             3             2             1
Protocol Violation             0             0             1
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100 Total
Hide Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Total of all reporting groups
Overall Number of Baseline Participants 403 137 136 676
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 403 participants 137 participants 136 participants 676 participants
55.6
(24 to 84)
56.8
(19 to 88)
57.4
(23 to 90)
56.2
(19 to 90)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
< 65 years 291 95 94 480
>=65 years 112 42 42 196
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
Female
156
  38.7%
56
  40.9%
63
  46.3%
275
  40.7%
Male
247
  61.3%
81
  59.1%
73
  53.7%
401
  59.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
White 380 129 129 638
Black 3 1 1 5
Hispanic 18 7 5 30
Other 2 0 1 3
Duration of Melanoma   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 403 participants 137 participants 136 participants 676 participants
5.09
(0.2 to 38.9)
4.34
(-0.0 to 35.9)
5.65
(0.3 to 31.2)
5.05
(-0.0 to 38.9)
[1]
Measure Description: Duration of melanoma is the number of years from date of initial diagnosis to the date of randomization. The randomization of 1 participant in the ipilumumab monotherapy cohort was prior to the initial diagnostic date. Data for 2 participants in the ipilimumab + gp100 cohort were missing.
Melanoma Stage   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
M0 5 1 4 10
M1a 37 14 11 62
M1b 76 22 23 121
M1c 285 100 98 483
[1]
Measure Description: The "M" in the TNM (tumor, node, metastasis) system refers to distant metastases—whether, and how far, the cancer has spread outside the original site. M0: There is no evidence that the cancer has spread beyond the original site. M1: The cancer has spread beyond the original site. M1a: The cancer has spread to other areas of skin, underneath the epidermis to the dermis (subcutaneous), or to lymph node(s). M1b: The cancer has spread to the lung(s) only. M1c: The cancer has spread to other organs and/or locations in the body with or without elevated LDH.
Prior Interleukin-2 Therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
No 314 105 103 522
Yes 89 32 33 154
Lactate Dehydrogenase   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 137 participants 136 participants 676 participants
>upper limit of normal (ULN) 149 53 52 254
<=ULN 252 84 81 417
unknown 2 0 3 5
[1]
Measure Description: Upper limit of normal (ULN) was 250 U/L for most assessments (some variation caused by tests performed at local laboratories).
1.Primary Outcome
Title Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
Hide Description OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 136
Median (95% Confidence Interval)
Unit of Measure: months
9.95
(8.48 to 11.50)
6.44
(5.49 to 8.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.55 to 0.85
Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
2.Secondary Outcome
Title Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy
Hide Description OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Median (95% Confidence Interval)
Unit of Measure: months
9.95
(8.48 to 11.50)
10.12
(8.02 to 13.80)
6.44
(5.49 to 8.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.51 to 0.87
Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7575
Comments [Not Specified]
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.83 to 1.30
Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
3.Secondary Outcome
Title 12-, 18-, and 24-Month Survival Rates
Hide Description The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.
Time Frame Month 12, Month 18, Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
12-Month Survival Rate
0.436
(0.386 to 0.485)
0.456
(0.370 to 0.541)
0.253
(0.181 to 0.329)
18-Month Survival Rate
0.300
(0.254 to 0.347)
0.332
(0.249 to 0.417)
0.163
(0.101 to 0.230)
24-Month Survival Rate
0.216
(0.172 to 0.261)
0.235
(0.160 to 0.315)
0.137
(0.080 to 0.200)
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study. Subjects who neither progressed nor died were censored at the date of the last tumor assessment.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Median (95% Confidence Interval)
Unit of Measure: months
2.76
(2.73 to 2.79)
2.86
(2.76 to 3.02)
2.76
(2.73 to 2.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.66 to 1.00
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.50 to 0.83
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
1.01 to 1.53
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
5.Secondary Outcome
Title Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
Hide Description PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Time Frame Week 12, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Median (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12
0.491
(0.441 to 0.539)
0.577
(0.489 to 0.655)
0.485
(0.396 to 0.567)
Week 24
0.164
(0.129 to 0.203)
0.240
(0.171 to 0.315)
0.100
(0.056 to 0.159)
6.Secondary Outcome
Title Time to Progression (TTP)
Hide Description TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.
Time Frame from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Median (95% Confidence Interval)
Unit of Measure: months
2.76
(2.73 to 2.79)
2.86
(2.76 to 3.02)
2.76
(2.73 to 2.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.66 to 1.00
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.50 to 0.83
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
1.01 to 1.53
Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
7.Secondary Outcome
Title Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Hide Description Investigator’s assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations >=4 weeks apart, no evidence of PD. PR: >=50% ↓ in sum of products of longest diameter & greatest perpendicular diameter of all target lesions compared to baseline by 2 observations >=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ >=25% in sum of products of longest diameter & greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of >= 1 new lesion.
Time Frame BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Measure Type: Number
Unit of Measure: participants
Complete Response 1 2 0
Partial Response 22 13 2
Stable Disease 58 24 13
Progressed Disease 239 70 89
Not Evaluated, Missing, or Unknown 83 28 32
8.Secondary Outcome
Title Determination of Best Overall Response Rate (BORR)
Hide Description Response was based on the investigators’ assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.
Time Frame Up to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.7
(3.7 to 8.4)
10.9
(6.3 to 17.4)
1.5
(0.2 to 5.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0433
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0402
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
9.Secondary Outcome
Title Time to Response
Hide Description Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.
Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Responder subjects in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 23 15 2
Mean (Full Range)
Unit of Measure: months
3.324
(2.10 to 5.59)
3.176
(2.60 to 5.52)
2.743
(2.69 to 2.79)
10.Secondary Outcome
Title Duration of Response
Hide Description Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).
Time Frame from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Responders only in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study. Patients who did not progress or died were censored at the date of their last tumor assessment.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 23 15 2
Median (95% Confidence Interval)
Unit of Measure: months
11.47 [1] 
(5.36 to NA)
NA [2] 
(28.09 to NA)
NA [3] 
(2.00 to NA)
[1]
Upper limit of 95% CI was not reached because most subjects were censored and the upper bound was not estimable.
[2]
Median duration of response was not reached because of the number of ongoing responses (ie, since most subjects did not progress-die, the median was not reached).
[3]
The limited number of responses (2) in the gp100 monotherapy group prevented a median duration from being reached.
11.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.
Time Frame Up to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 403 137 136
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.1
(16.3 to 24.3)
28.5
(21.1 to 36.8)
11.0
(6.3 to 17.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0179
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0429
Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
12.Secondary Outcome
Title Delayed Response (Response Beyond Week 24)
Hide Description Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.
Time Frame from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
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Hide Analysis Population Description
Number of subjects with BOR of PR/SD (80 subjects ipi + gp100 , 37 ipi , 15 gp100) plus number of subjects with BOR of PD that had subsequent evaluation (8 ipi + gp100, 3 ipi, 3 gp100).
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 88 40 18
Measure Type: Number
Unit of Measure: participants
Complete Response Beyond Week 24 1 3 0
Partial Response Beyond Week 24 3 2 0
Stable Disease Beyond Week 24 3 0 0
13.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12
Hide Description The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).
Time Frame Baseline (Day 1, Cycle1), Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication. N=number of participants analyzed, n=number of participants with measure at given time points.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 381 131 131
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Global QOL (n=226, 83, 77)
-7.4
(-10.4 to -4.3)
-8.8
(-13.5 to -4.1)
-10.4
(-15.3 to -5.5)
Physical (n=226 83, 78)
-6.2
(-8.9 to -3.4)
-5.1
(-9.4 to -0.8)
-10.1
(-14.5 to -5.7)
Role Change (n=226, 83, 78)
-9.3
(-13.4 to -5.3)
-10.5
(-16.8 to -4.1)
-13.7
(-20.2 to -7.2)
Cognitive (n=226, 83, 78)
-3.1
(-5.8 to -0.3)
-4.3
(-8.6 to 0.0)
-3.4
(-7.8 to 1.0)
Emotional (n=227, 83, 78)
-1.5
(-4.2 to 1.1)
-3.6
(-7.7 to 0.6)
-1.5
(-5.8 to 2.7)
Social (n=227, 83, 76)
-5.6
(-9.2 to -2.0)
-7.5
(-13.2 to -1.9)
-4.2
(-10.1 to 1.8)
Fatigue (n=226, 82, 78)
10.6
(7.0 to 14.1)
12.5
(7.0 to 18.1)
14.5
(8.8 to 20.2)
Nausea and Vomiting (n=226, 83, 78)
4.6
(1.9 to 7.3)
3.1
(-1.0 to 7.3)
4.4
(0.1 to 8.7)
Pain (n=227, 83, 78)
5.6
(2.0 to 9.3)
7.9
(2.2 to 13.6)
11.9
(6.0 to 17.7)
Dyspnea (n=222, 81, 77)
3.5
(0.0 to 6.9)
5.3
(-0.1 to 10.7)
9.1
(3.6 to 14.6)
Sleep Disturbance (n=225, 83, 76)
6.5
(2.3 to 10.7)
10.1
(3.6 to 16.6)
11.0
(4.3 to 17.8)
Appetite Loss (n=225, 83, 78)
8.5
(4.4 to 12.5)
11.6
(5.3 to 17.9)
10.3
(3.8 to 16.8)
Constipation (n=225, 83, 77)
5.2
(1.7 to 8.7)
1.9
(-3.5 to 7.2)
11.8
(6.2 to 17.4)
Diarrhea (n=223, 82, 78)
6.4
(2.8 to 10.1)
9.1
(3.4 to 14.7)
2.1
(-3.7 to 7.9)
Financial Impact (n=226, 83, 76)
0.0
(-3.2 to 3.2)
3.1
(-1.9 to 8.1)
1.7
(-3.5 to 6.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Global quality of life change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2805
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-2.5 to 8.6
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Global quality of life change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6300
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-5.0 to 8.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Global quality of life change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6026
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-3.9 to 6.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Physical change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1219
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-1.1 to 8.9
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Physical change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0978
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-0.9 to 11.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Physical change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6590
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-6.0 to 3.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Role change, change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2480
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-3.0 to 11.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Role change, change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4742
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-5.6 to 12.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Role change, change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7597
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-6.1 to 8.3
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Cognitive change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9119
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-4.7 to 5.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Cognitive change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7616
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-6.9 to 5.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Cognitive change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6266
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-3.6 to 6.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Emotional change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9984
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-4.8 to 4.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Emotional change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4873
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-7.8 to 3.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Emotional change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3938
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-2.7 to 6.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Social change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6695
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-8.1 to 5.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Social change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4041
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-11.3 to 4.6
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Social change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5538
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-4.5 to 8.3
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Fatigue change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2259
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-10.3 to 2.4
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Fatigue change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6168
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-9.6 to 5.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Fatigue change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5329
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-8.2 to 4.3
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Nausea and Vomiting change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9397
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-4.7 to 5.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Nausea and Vomiting change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6716
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-7.1 to 4.6
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Nausea and Vomiting change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5497
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-3.3 to 6.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Pain change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0625
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.3
Confidence Interval (2-Sided) 95%
-12.8 to 0.3
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Pain change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3214
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-11.9 to 3.9
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Pain change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4898
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-8.7 to 4.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Dyspnea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0761
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-11.8 to 0.6
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Dyspnea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3187
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-11.2 to 3.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Dyspnea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5548
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-7.9 to 4.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Sleep disturbance change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2450
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-12.1 to 3.1
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Sleep disturbance change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8464
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-10.0 to 8.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Sleep Disturbance change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3351
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-10.9 to 3.7
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Appetite loss change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6291
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-9.1 to 5.5
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Appetite Loss change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7675
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-7.4 to 10.1
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Appetite Loss change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3911
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-10.2 to 4.0
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Constipation change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0431
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.5
Confidence Interval (2-Sided) 95%
-12.9 to -0.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Constipation change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.9
Confidence Interval (2-Sided) 95%
-17.4 to -2.4
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Constipation change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2796
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
-2.8 to 9.5
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Diarrhea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1940
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-2.2 to 10.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Diarrhea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0821
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
-0.9 to 14.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Diarrhea change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4169
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-9.0 to 3.8
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 43 Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
Comments Financial Impact change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5717
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-7.5 to 4.2
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 44 Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Ipilimumab Monotherapy, gp100
Comments Financial Impact change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6949
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-5.6 to 8.4
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
Show Statistical Analysis 45 Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, Ipilimumab Monotherapy
Comments Financial Impact change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2849
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-8.8 to 2.6
Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
14.Secondary Outcome
Title Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Hide Description An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.
Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: percentage of participants
Any On-Study AE 98.4 96.9 97.0
Severe (>=Grade 3) On-Study AEs 50.8 55.0 52.3
Serious On-Study AEs 40.8 42.0 39.4
Related On-Study AEs 88.9 80.2 78.8
On-Study AEs Leading to Discontinuation 9.2 13.0 3.8
AEs with Outcome of Death 6.1 9.9 6.1
Related AE with Outcome of Death 2.1 3.1 1.5
15.Secondary Outcome
Title Percentage of Participants With Immune-Related Adverse Events (irAEs)
Hide Description An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.
Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
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Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: percentage of participants
Any On-Study irAEs 58.2 61.1 31.8
On-Study Severe irAEs 11.3 15.3 3.0
On-Study Serious irAEs 10.5 13.0 0.8
On-Study irAEs Leading to Discontinuation 5.8 8.4 0.8
Death Due to irAEs 1.3 1.5 0
Gastrointestinal irAEs (any grade) 32.1 29.0 14.4
Severe (>= Grade 3) Gastrointestinal irAEs 6.3 7.6 0.8
Liver irAEs (any grade) 2.1 3.8 4.5
Severe (>= Grade 3) Liver irAEs 1.1 0.8 2.3
Endocrine irAEs (any grade) 3.9 7.6 1.5
Severe (>= Grade 3) Endocrine irAEs 1.1 3.8 0
Skin irAEs (any grade) 40.0 43.5 16.7
Severe (>= Grade 3) Skin irAEs 2.4 1.5 0
Neurological irAEs (any grade) 0.5 0 0
Severe (>= Grade 3) Neurological irAEs 0.5 0 0
Other irAEs (any grade) 3.2 4.6 2.3
Severe (>= Grade 3) Other irAEs 1.6 2.3 0.8
16.Secondary Outcome
Title Percentage of Participants With Worst On-Study Hematological Abnormalities
Hide Description ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Time Frame On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
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Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: percentage of participants
Hemoglobin, Grade 0 (n=352, 121, 126) 48.9 44.6 46.8
Hemoglobin, Grade 1 (n=352, 121, 126) 37.2 40.5 34.1
Hemoglobin, Grade 2 (n=352, 121, 126) 12.2 14.0 15.1
Hemoglobin, Grade 3 (n=352, 121, 126) 1.7 0.8 4.0
Hemoglobin, Grade 4 (n=352, 121, 126) 0 0 0
Hemoglobin, Grade 1-4 (n=352, 121, 126) 51.1 55.4 53.2
Hemoglobin, Grade 3-4 (n=352, 121, 126) 1.7 0.8 4.0
White Blood Cells, Grade 0 (n=352, 121, 126) 97.2 95.9 92.9
White Blood Cells, Grade 1 (n=352, 121, 126) 1.4 1.7 5.6
White Blood Cells, Grade 2 (n=352, 121, 126) 1.1 2.5 1.6
White Blood Cells, Grade 3 (n=352, 121, 126) 0.3 0 0
White Blood Cells, Grade 4 (n=352, 121, 126) 0 0 0
White Blood Cells, Grade 1-4 (n=352, 121, 126) 2.8 4.1 7.1
White Blood Cells, Grade 3-4 (n=352, 121, 126) 0.3 0 0
ANC, Grade 0 (n=352, 121, 126) 95.5 93.4 96.0
ANC, Grade 1 (n=352, 121, 126) 2.8 3.3 2.4
ANC, Grade 2 (n=352, 121, 126) 0.9 2.5 0.8
ANC, Grade 3 (n=352, 121, 126) 0.6 0.8 0.8
ANC, Grade 4 (n=352, 121, 126) 0.3 0 0
ANC, Grade 1-4 (n=352, 121, 126) 4.5 6.6 4.0
ANC, Grade 3-4 (n=352, 121, 126) 0.9 0.8 0.8
Platelet Count, Grade 0 (n=349, 121, 126) 94.6 90.1 91.3
Platelet Count, Grade 1 (n=349, 121, 126) 4.9 9.1 8.7
Platelet Count, Grade 2 (n=349, 121, 126) 0.6 0.8 0
Platelet Count, Grade 3 (n=349, 121, 126) 0 0 0
Platelet Count, Grade 4 (n=349, 121, 126) 0 0 0
Platelet Count, Grade 1-4 (n=349, 121, 126) 5.4 9.9 8.7
Platelet Count, Grade 3-4 (n=349, 121, 126) 0 0 0
Lymphocytes (absolute), Grade 0 (n=352, 121, 126) 33.8 34.7 22.2
Lymphocytes (absolute), Grade 1 (n=352, 121, 126) 46.3 47.9 42.9
Lymphocytes (absolute), Grade 2 (n=352, 121, 126) 15.1 14.9 25.4
Lymphocytes (absolute), Grade 3 (n=352, 121, 126) 4.3 2.5 9.5
Lymphocytes (absolute), Grade 4 (n=352, 121, 126) 0.6 0 0
Lymphocytes (absolute), Grade 1-4(n=352, 121, 126) 66.2 65.3 77.8
Lymphocytes (absolute), Grade 3-4(n=352, 121, 126) 4.8 2.5 9.5
17.Secondary Outcome
Title Percentage of Participants With Worst On-Study Liver Abnormalities
Hide Description ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: percentage of participants
ALT, Grade 0 (n=352, 121, 126) 83.2 76.0 84.9
ALT, Grade 1 (n=352, 121, 126) 13.6 19.0 12.7
ALT, Grade 2 (n=352, 121, 126) 2.0 3.3 1.6
ALT, Grade 3 (n=352, 121, 126) 0.9 1.7 0.8
ALT, Grade 4 (n=352, 121, 126) 0.3 0 0
ALT, Grade 1-4 (n=352, 121, 126) 16.8 24.0 15.1
ALT, Grade 3-4 (n=352, 121, 126) 1.1 1.7 0.8
AST, Grade 0 (n=352, 121, 126) 80.4 71.9 81.7
AST, Grade 1 (n=352, 121, 126) 16.5 23.1 15.1
AST, Grade 2 (n=352, 121, 126) 1.4 3.3 2.4
AST, Grade 3 (n=352, 121, 126) 1.4 1.7 0.8
AST, Grade 4 (n=352, 121, 126) 0.3 0 0
AST, Grade 1-4 (n=352, 121, 126) 19.6 28.1 18.3
AST, Grade 3-4 (n=352, 121, 126) 1.7 1.7 0.8
Total Bilirubin, Grade 0 (n=353, 121, 127) 95.5 93.4 98.4
Total Bilirubin, Grade 1 (n=353, 121, 127) 2.5 4.1 0.8
Total Bilirubin, Grade 2 (n=353, 121, 127) 1.4 1.7 0.8
Total Bilirubin, Grade 3 (n=353, 121, 127) 0.6 0.8 0
Total Bilirubin, Grade 4 (n=353, 121, 127) 0 0 0
Total Bilirubin, Grade 1-4 (n=353, 121, 127) 4.5 6.6 1.6
Total Bilirubin, Grade 3-4 (n=353, 121, 127) 0.6 0.8 0
Alkaline Phosphatase, Grade 0 (n=353, 121, 128) 73.7 71.9 71.1
Alkaline Phosphatase, Grade 1 (n=353, 121, 128) 19.8 20.7 24.2
Alkaline Phosphatase, Grade 2 (n=353, 121, 128) 4.8 4.1 3.9
Alkaline Phosphatase, Grade 3 (n=353, 121, 128) 1.7 3.3 0.8
Alkaline Phosphatase, Grade 4 (n=353, 121, 128) 0 0 0
Alkaline Phosphatase, Grade 1-4 (n=353, 121, 128) 26.3 28.1 28.9
Alkaline Phosphatase, Grade 3-4 (n=353, 121, 128) 1.7 3.3 0.8
18.Secondary Outcome
Title Percentage of Participants With Worst On-Study Renal Abnormalities
Hide Description CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: percentage of participants
Creatinine, Grade 0 (n=353, 121, 128) 89.5 88.4 88.3
Creatinine, Grade 1 (n=353, 121, 128) 8.8 9.9 9.4
Creatinine, Grade 2 (n=353, 121, 128) 1.4 1.7 2.3
Creatinine, Grade 3 (n=353, 121, 128) 0.3 0 0
Creatinine, Grade 4 (n=353, 121, 128) 0 0 0
Creatinine, Grade 1-4 (n=353, 121, 128) 10.5 11.6 11.7
Creatinine, Grade 3-4 (n=353, 121, 128) 0.3 0 0
19.Secondary Outcome
Title Clinically Meaningful Changes in Vital Signs and Physical Examinations
Hide Description Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.
Time Frame vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter
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Hide Analysis Population Description
All subjects who received at least 1 dose or any partial dose of study medication.
Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
Hide Arm/Group Description:
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
Overall Number of Participants Analyzed 380 131 132
Measure Type: Number
Unit of Measure: participants
Clinically Meaningful Vital Sign Changes 0 0 0
Clinically Meaningful Physical Examination Changes 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
Hide Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
All-Cause Mortality
Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   55/131 (41.98%)   155/380 (40.79%)   52/132 (39.39%) 
Blood and lymphatic system disorders       
ANAEMIA  1  4/131 (3.05%)  5/380 (1.32%)  5/132 (3.79%) 
HAEMOLYTIC ANAEMIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
LEUKOCYTOSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
NEUTROPENIA  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
THROMBOCYTOPENIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
Cardiac disorders       
ATRIAL FIBRILLATION  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
CARDIAC FAILURE  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
CARDIAC FAILURE CONGESTIVE  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
CARDIAC TAMPONADE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
CARDIOPULMONARY FAILURE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
CORONARY ARTERY DISEASE  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
PERICARDIAL EFFUSION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
SUPRAVENTRICULAR TACHYCARDIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
TACHYCARDIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Endocrine disorders       
ADRENAL INSUFFICIENCY  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
HYPOGONADISM  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HYPOPHYSITIS  1  2/131 (1.53%)  1/380 (0.26%)  0/132 (0.00%) 
HYPOPITUITARISM  1  2/131 (1.53%)  3/380 (0.79%)  0/132 (0.00%) 
HYPOTHYROIDISM  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Eye disorders       
IRIDOCYCLITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Gastrointestinal disorders       
ABDOMINAL DISTENSION  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
ABDOMINAL PAIN  1  2/131 (1.53%)  4/380 (1.05%)  5/132 (3.79%) 
ABDOMINAL PAIN UPPER  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
ABDOMINAL WALL MASS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
ASCITES  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
COLITIS  1  7/131 (5.34%)  14/380 (3.68%)  0/132 (0.00%) 
CONSTIPATION  1  0/131 (0.00%)  3/380 (0.79%)  1/132 (0.76%) 
DIARRHOEA  1  6/131 (4.58%)  16/380 (4.21%)  0/132 (0.00%) 
DYSPHAGIA  1  1/131 (0.76%)  0/380 (0.00%)  1/132 (0.76%) 
GASTRITIS  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
GASTROINTESTINAL PERFORATION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HAEMATOCHEZIA  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
HAEMORRHOIDS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
ILEUS  1  0/131 (0.00%)  3/380 (0.79%)  0/132 (0.00%) 
INTESTINAL HAEMORRHAGE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
INTESTINAL OBSTRUCTION  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
INTESTINAL PERFORATION  1  0/131 (0.00%)  3/380 (0.79%)  0/132 (0.00%) 
INTUSSUSCEPTION  1  0/131 (0.00%)  0/380 (0.00%)  2/132 (1.52%) 
LARGE INTESTINAL OBSTRUCTION  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
LARGE INTESTINE PERFORATION  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
NAUSEA  1  2/131 (1.53%)  6/380 (1.58%)  4/132 (3.03%) 
PERITONITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PROCTALGIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
RECTAL STENOSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
SMALL INTESTINAL OBSTRUCTION  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
VOMITING  1  3/131 (2.29%)  7/380 (1.84%)  3/132 (2.27%) 
General disorders       
ADVERSE EVENT  1  1/131 (0.76%)  3/380 (0.79%)  0/132 (0.00%) 
ASTHENIA  1  3/131 (2.29%)  4/380 (1.05%)  1/132 (0.76%) 
CHEST PAIN  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
CHILLS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
DISEASE PROGRESSION  1  2/131 (1.53%)  6/380 (1.58%)  3/132 (2.27%) 
FATIGUE  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
GAIT DISTURBANCE  1  1/131 (0.76%)  0/380 (0.00%)  1/132 (0.76%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/131 (0.00%)  2/380 (0.53%)  2/132 (1.52%) 
GENERALISED OEDEMA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HERNIA OBSTRUCTIVE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
INFLUENZA LIKE ILLNESS  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
INFUSION RELATED REACTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
INJECTION SITE REACTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
INJECTION SITE ULCER  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
MULTI-ORGAN FAILURE  1  0/131 (0.00%)  2/380 (0.53%)  2/132 (1.52%) 
OEDEMA  1  2/131 (1.53%)  1/380 (0.26%)  0/132 (0.00%) 
OEDEMA PERIPHERAL  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
PAIN  1  1/131 (0.76%)  3/380 (0.79%)  0/132 (0.00%) 
PYREXIA  1  2/131 (1.53%)  7/380 (1.84%)  1/132 (0.76%) 
Hepatobiliary disorders       
ACUTE HEPATIC FAILURE  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
BILE DUCT OBSTRUCTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
CHOLECYSTITIS  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HEPATIC FAILURE  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
HEPATITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HYPERBILIRUBINAEMIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
JAUNDICE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
JAUNDICE CHOLESTATIC  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Infections and infestations       
APPENDICITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
BACTERAEMIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
BRONCHOPNEUMONIA  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
CATHETER RELATED INFECTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
CELLULITIS  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
CYSTITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
ENTEROCOCCAL BACTERAEMIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
ERYSIPELAS  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
EYELID INFECTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
GASTROINTESTINAL INFECTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HEPATITIS A  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HEPATITIS B  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
INFECTION  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
LOCALISED INFECTION  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
MENINGITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PERIRECTAL ABSCESS  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
PNEUMONIA  1  2/131 (1.53%)  8/380 (2.11%)  3/132 (2.27%) 
POSTOPERATIVE WOUND INFECTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PSEUDOMONAL SEPSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
SEPSIS  1  3/131 (2.29%)  4/380 (1.05%)  0/132 (0.00%) 
SEPTIC SHOCK  1  1/131 (0.76%)  1/380 (0.26%)  1/132 (0.76%) 
URINARY TRACT INFECTION  1  0/131 (0.00%)  2/380 (0.53%)  3/132 (2.27%) 
Injury, poisoning and procedural complications       
ACCIDENTAL OVERDOSE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
FEMORAL NECK FRACTURE  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
GASTROINTESTINAL STOMA COMPLICATION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HIP FRACTURE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PROCEDURAL COMPLICATION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Investigations       
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
BLOOD CORTICOTROPHIN DECREASED  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
INTERNATIONAL NORMALISED RATIO ABNORMAL  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
URINE OUTPUT DECREASED  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
Metabolism and nutrition disorders       
DECREASED APPETITE  1  2/131 (1.53%)  3/380 (0.79%)  1/132 (0.76%) 
DEHYDRATION  1  1/131 (0.76%)  8/380 (2.11%)  4/132 (3.03%) 
FAILURE TO THRIVE  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
HYPOALBUMINAEMIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HYPOGLYCAEMIA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HYPONATRAEMIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HYPOPHAGIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
MALNUTRITION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
TUMOUR LYSIS SYNDROME  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
BACK PAIN  1  0/131 (0.00%)  2/380 (0.53%)  2/132 (1.52%) 
BONE PAIN  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
MUSCULAR WEAKNESS  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
MUSCULOSKELETAL PAIN  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
NECK PAIN  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
PAIN IN EXTREMITY  1  0/131 (0.00%)  3/380 (0.79%)  1/132 (0.76%) 
PATHOLOGICAL FRACTURE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
POLYMYALGIA RHEUMATICA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
BASAL CELL CARCINOMA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
CANCER PAIN  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
INTRACRANIAL TUMOUR HAEMORRHAGE  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
MALIGNANT ASCITES  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
MALIGNANT MELANOMA  1  0/131 (0.00%)  3/380 (0.79%)  1/132 (0.76%) 
MALIGNANT NEOPLASM PROGRESSION  1  0/131 (0.00%)  3/380 (0.79%)  0/132 (0.00%) 
METASTASES TO BREAST  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
METASTASES TO CENTRAL NERVOUS SYSTEM  1  2/131 (1.53%)  3/380 (0.79%)  0/132 (0.00%) 
METASTASES TO SPINE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
METASTATIC MALIGNANT MELANOMA  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
METASTATIC NEOPLASM  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
METASTATIC PAIN  1  1/131 (0.76%)  3/380 (0.79%)  0/132 (0.00%) 
TUMOUR HAEMORRHAGE  1  0/131 (0.00%)  1/380 (0.26%)  2/132 (1.52%) 
TUMOUR PAIN  1  2/131 (1.53%)  2/380 (0.53%)  1/132 (0.76%) 
Nervous system disorders       
APHASIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
ATAXIA  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
BRAIN OEDEMA  1  1/131 (0.76%)  2/380 (0.53%)  0/132 (0.00%) 
CEREBRAL HAEMORRHAGE  1  0/131 (0.00%)  0/380 (0.00%)  2/132 (1.52%) 
CEREBROVASCULAR ACCIDENT  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
COMA  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
CONVULSION  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
DEPRESSED LEVEL OF CONSCIOUSNESS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
DIZZINESS  1  0/131 (0.00%)  0/380 (0.00%)  2/132 (1.52%) 
DYSARTHRIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
EPIDURITIS  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
GUILLAIN-BARRE SYNDROME  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HAEMORRHAGE INTRACRANIAL  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
HEADACHE  1  0/131 (0.00%)  2/380 (0.53%)  1/132 (0.76%) 
HYDROCEPHALUS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HYPOAESTHESIA  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
INTRACRANIAL PRESSURE INCREASED  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
LETHARGY  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
MENINGEAL DISORDER  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
MYOCLONUS  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
SPINAL CORD COMPRESSION  1  1/131 (0.76%)  3/380 (0.79%)  0/132 (0.00%) 
SYNCOPE  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
Psychiatric disorders       
ANXIETY  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
CONFUSIONAL STATE  1  2/131 (1.53%)  1/380 (0.26%)  1/132 (0.76%) 
DELIRIUM  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
MENTAL STATUS CHANGES  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
Renal and urinary disorders       
ATONIC URINARY BLADDER  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
BLADDER PAIN  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
GLOMERULONEPHRITIS  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
HYDRONEPHROSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
RENAL FAILURE  1  3/131 (2.29%)  3/380 (0.79%)  0/132 (0.00%) 
RENAL FAILURE ACUTE  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
RENAL TUBULAR NECROSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
URETERIC OBSTRUCTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
URINARY INCONTINENCE  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
URINARY RETENTION  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
Reproductive system and breast disorders       
BREAST MASS  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
PELVIC PAIN  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
ACUTE PULMONARY OEDEMA  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
ACUTE RESPIRATORY DISTRESS SYNDROME  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
BRONCHIAL OBSTRUCTION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
COUGH  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
DYSPNOEA  1  3/131 (2.29%)  2/380 (0.53%)  7/132 (5.30%) 
HAEMOPTYSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
HAEMOTHORAX  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
PAINFUL RESPIRATION  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
PLEURAL EFFUSION  1  2/131 (1.53%)  5/380 (1.32%)  4/132 (3.03%) 
PLEURITIC PAIN  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PNEUMONITIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
PULMONARY EMBOLISM  1  1/131 (0.76%)  3/380 (0.79%)  2/132 (1.52%) 
PULMONARY HAEMORRHAGE  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
RESPIRATORY ARREST  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
RESPIRATORY DEPRESSION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
RESPIRATORY FAILURE  1  1/131 (0.76%)  2/380 (0.53%)  0/132 (0.00%) 
SLEEP APNOEA SYNDROME  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
Skin and subcutaneous tissue disorders       
LEUKOCYTOCLASTIC VASCULITIS  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
RASH  1  0/131 (0.00%)  2/380 (0.53%)  0/132 (0.00%) 
RASH GENERALISED  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
RASH PRURITIC  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
TOXIC EPIDERMAL NECROLYSIS  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
Vascular disorders       
ANGIOPATHY  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
ARTERIAL THROMBOSIS LIMB  1  1/131 (0.76%)  0/380 (0.00%)  0/132 (0.00%) 
DEEP VEIN THROMBOSIS  1  2/131 (1.53%)  5/380 (1.32%)  1/132 (0.76%) 
HAEMATOMA  1  0/131 (0.00%)  1/380 (0.26%)  1/132 (0.76%) 
HYPERTENSIVE CRISIS  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
HYPOTENSION  1  3/131 (2.29%)  1/380 (0.26%)  2/132 (1.52%) 
LYMPHOEDEMA  1  0/131 (0.00%)  0/380 (0.00%)  1/132 (0.76%) 
SUPERIOR VENA CAVAL OCCLUSION  1  0/131 (0.00%)  1/380 (0.26%)  0/132 (0.00%) 
THROMBOSIS  1  1/131 (0.76%)  1/380 (0.26%)  0/132 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   124/131 (94.66%)   362/380 (95.26%)   124/132 (93.94%) 
Blood and lymphatic system disorders       
ANAEMIA  1  14/131 (10.69%)  36/380 (9.47%)  22/132 (16.67%) 
Gastrointestinal disorders       
ABDOMINAL DISTENSION  1  0/131 (0.00%)  13/380 (3.42%)  9/132 (6.82%) 
ABDOMINAL PAIN  1  20/131 (15.27%)  64/380 (16.84%)  18/132 (13.64%) 
ABDOMINAL PAIN UPPER  1  7/131 (5.34%)  17/380 (4.47%)  11/132 (8.33%) 
CONSTIPATION  1  27/131 (20.61%)  79/380 (20.79%)  34/132 (25.76%) 
DIARRHOEA  1  41/131 (31.30%)  142/380 (37.37%)  26/132 (19.70%) 
DYSPEPSIA  1  2/131 (1.53%)  14/380 (3.68%)  10/132 (7.58%) 
FLATULENCE  1  3/131 (2.29%)  9/380 (2.37%)  8/132 (6.06%) 
NAUSEA  1  44/131 (33.59%)  127/380 (33.42%)  49/132 (37.12%) 
VOMITING  1  30/131 (22.90%)  71/380 (18.68%)  27/132 (20.45%) 
General disorders       
ADVERSE EVENT  1  4/131 (3.05%)  22/380 (5.79%)  5/132 (3.79%) 
ASTHENIA  1  6/131 (4.58%)  37/380 (9.74%)  17/132 (12.88%) 
CHILLS  1  9/131 (6.87%)  23/380 (6.05%)  7/132 (5.30%) 
FATIGUE  1  55/131 (41.98%)  137/380 (36.05%)  41/132 (31.06%) 
INFLUENZA LIKE ILLNESS  1  7/131 (5.34%)  20/380 (5.26%)  3/132 (2.27%) 
INJECTION SITE ERYTHEMA  1  1/131 (0.76%)  26/380 (6.84%)  5/132 (3.79%) 
INJECTION SITE INDURATION  1  0/131 (0.00%)  25/380 (6.58%)  4/132 (3.03%) 
INJECTION SITE PAIN  1  2/131 (1.53%)  25/380 (6.58%)  13/132 (9.85%) 
INJECTION SITE REACTION  1  2/131 (1.53%)  109/380 (28.68%)  26/132 (19.70%) 
OEDEMA PERIPHERAL  1  12/131 (9.16%)  47/380 (12.37%)  22/132 (16.67%) 
PAIN  1  6/131 (4.58%)  23/380 (6.05%)  15/132 (11.36%) 
PYREXIA  1  15/131 (11.45%)  74/380 (19.47%)  23/132 (17.42%) 
Infections and infestations       
URINARY TRACT INFECTION  1  8/131 (6.11%)  8/380 (2.11%)  4/132 (3.03%) 
Investigations       
WEIGHT DECREASED  1  8/131 (6.11%)  33/380 (8.68%)  12/132 (9.09%) 
Metabolism and nutrition disorders       
DECREASED APPETITE  1  33/131 (25.19%)  85/380 (22.37%)  29/132 (21.97%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  12/131 (9.16%)  30/380 (7.89%)  14/132 (10.61%) 
BACK PAIN  1  9/131 (6.87%)  32/380 (8.42%)  16/132 (12.12%) 
MUSCULOSKELETAL CHEST PAIN  1  7/131 (5.34%)  7/380 (1.84%)  2/132 (1.52%) 
MUSCULOSKELETAL PAIN  1  5/131 (3.82%)  30/380 (7.89%)  10/132 (7.58%) 
MYALGIA  1  8/131 (6.11%)  28/380 (7.37%)  4/132 (3.03%) 
PAIN IN EXTREMITY  1  9/131 (6.87%)  51/380 (13.42%)  19/132 (14.39%) 
Nervous system disorders       
DIZZINESS  1  5/131 (3.82%)  27/380 (7.11%)  13/132 (9.85%) 
HEADACHE  1  19/131 (14.50%)  64/380 (16.84%)  18/132 (13.64%) 
Psychiatric disorders       
ANXIETY  1  5/131 (3.82%)  31/380 (8.16%)  9/132 (6.82%) 
INSOMNIA  1  16/131 (12.21%)  33/380 (8.68%)  15/132 (11.36%) 
Respiratory, thoracic and mediastinal disorders       
COUGH  1  21/131 (16.03%)  55/380 (14.47%)  17/132 (12.88%) 
DYSPNOEA  1  16/131 (12.21%)  45/380 (11.84%)  20/132 (15.15%) 
Skin and subcutaneous tissue disorders