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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00094653
First received: October 21, 2004
Last updated: June 29, 2011
Last verified: June 2011
Results First Received: April 22, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Melanoma
Metastases
Interventions: Drug: MDX-010 (anti-CTLA4) monoclonal antibody
Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 1783 participants who enrolled and were screened for study participation, a total of 676 subjects were randomized.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Participant Flow:   Overall Study
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
STARTED     403     137     136  
Treated     381     131     131  
COMPLETED     82     31     10  
NOT COMPLETED     321     106     126  
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  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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 Total of all reporting groups

Baseline Measures
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100     Total  
Number of Participants  
[units: participants]
  403     137     136     676  
Age  
[units: years]
Mean ( Full Range )
  55.6  
  ( 24 to 84 )  
  56.8  
  ( 19 to 88 )  
  57.4  
  ( 23 to 90 )  
  56.2  
  ( 19 to 90 )  
Age, Customized  
[units: participants]
       
< 65 years     291     95     94     480  
>=65 years     112     42     42     196  
Gender  
[units: participants]
       
Female     156     56     63     275  
Male     247     81     73     401  
Race/Ethnicity, Customized  
[units: 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]
[units: years]
Mean ( Full Range )
  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 )  
Melanoma Stage [2]
[units: Participants]
       
M0     5     1     4     10  
M1a     37     14     11     62  
M1b     76     22     23     121  
M1c     285     100     98     483  
Prior Interleukin-2 Therapy  
[units: Participants]
       
No     314     105     103     522  
Yes     89     32     33     154  
Lactate Dehydrogenase [3]
[units: Participants]
       
>upper limit of normal (ULN)     149     53     52     254  
<=ULN     252     84     81     417  
unknown     2     0     3     5  
[1] 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.
[2] 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.
[3] Upper limit of normal (ULN) was 250 U/L for most assessments (some variation caused by tests performed at local laboratories).



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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   [ Time Frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) ]

Measure Type Primary
Measure 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
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 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.

Measured Values
    Ipilimumab Plus gp100     gp100  
Number of Participants Analyzed  
[units: participants]
  403     136  
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  
[units: months]
Median ( 95% Confidence Interval )
  9.95  
  ( 8.48 to 11.50 )  
  6.44  
  ( 5.49 to 8.71 )  


Statistical Analysis 1 for 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
Groups [1] All groups
Method [2] Stratified Log Rank
P Value [3] 0.0004
Hazard Ratio (HR) [4] 0.68
95% Confidence Interval ( 0.55 to 0.85 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   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   [ Time Frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) ]

Measure Type Secondary
Measure 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
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
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  
[units: months]
Median ( 95% Confidence Interval )
  9.95  
  ( 8.48 to 11.50 )  
  10.12  
  ( 8.02 to 13.80 )  
  6.44  
  ( 5.49 to 8.71 )  


Statistical Analysis 1 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] Stratified Log Rank
P Value [3] 0.0026
Hazard Ratio (HR) [4] 0.66
95% Confidence Interval ( 0.51 to 0.87 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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).

Statistical Analysis 2 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] Stratified Log Rank
P Value [3] 0.7575
Hazard Ratio (HR) [4] 1.04
95% Confidence Interval ( 0.83 to 1.30 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   12-, 18-, and 24-Month Survival Rates   [ Time Frame: Month 12, Month 18, Month 24 ]

Measure Type Secondary
Measure Title 12-, 18-, and 24-Month Survival Rates
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
12-, 18-, and 24-Month Survival Rates  
[units: probability]
Number ( 95% Confidence Interval )
     
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 )  

No statistical analysis provided for 12-, 18-, and 24-Month Survival Rates



4.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) ]

Measure Type Secondary
Measure Title Progression Free Survival (PFS)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Progression Free Survival (PFS)  
[units: months]
Median ( 95% Confidence Interval )
  2.76  
  ( 2.73 to 2.79 )  
  2.86  
  ( 2.76 to 3.02 )  
  2.76  
  ( 2.73 to 2.83 )  


Statistical Analysis 1 for Progression Free Survival (PFS)
Groups [1] Ipilimumab Plus gp100 vs. gp100
Hazard Ratio (HR) [2] 0.81
95% Confidence Interval ( 0.66 to 1.00 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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).

Statistical Analysis 2 for Progression Free Survival (PFS)
Groups [1] Ipilimumab Monotherapy vs. gp100
Hazard Ratio (HR) [2] 0.64
95% Confidence Interval ( 0.50 to 0.83 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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).

Statistical Analysis 3 for Progression Free Survival (PFS)
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Hazard Ratio (HR) [2] 1.25
95% Confidence Interval ( 1.01 to 1.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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:   Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24   [ Time Frame: Week 12, Week 24 ]

Measure Type Secondary
Measure Title Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24  
[units: percentage of participants]
Median ( 95% Confidence Interval )
     
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 )  

No statistical analysis provided for Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24



6.  Secondary:   Time to Progression (TTP)   [ 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]) ]

Measure Type Secondary
Measure Title Time to Progression (TTP)
Measure 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])  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Time to Progression (TTP)  
[units: months]
Median ( 95% Confidence Interval )
  2.76  
  ( 2.73 to 2.79 )  
  2.86  
  ( 2.76 to 3.02 )  
  2.76  
  ( 2.73 to 2.83 )  


Statistical Analysis 1 for Time to Progression (TTP)
Groups [1] Ipilimumab Plus gp100 vs. gp100
Hazard Ratio (HR) [2] 0.81
95% Confidence Interval ( 0.66 to 1.00 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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).

Statistical Analysis 2 for Time to Progression (TTP)
Groups [1] Ipilimumab Monotherapy vs. gp100
Hazard Ratio (HR) [2] 0.64
95% Confidence Interval ( 0.50 to 0.83 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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).

Statistical Analysis 3 for Time to Progression (TTP)
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Hazard Ratio (HR) [2] 1.25
95% Confidence Interval ( 1.01 to 1.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  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:   Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)   [ Time Frame: BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1. ]

Measure Type Secondary
Measure Title Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)  
[units: 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  

No statistical analysis provided for Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)



8.  Secondary:   Determination of Best Overall Response Rate (BORR)   [ Time Frame: Up to week 24 ]

Measure Type Secondary
Measure Title Determination of Best Overall Response Rate (BORR)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Determination of Best Overall Response Rate (BORR)  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  5.7  
  ( 3.7 to 8.4 )  
  10.9  
  ( 6.3 to 17.4 )  
  1.5  
  ( 0.2 to 5.2 )  


Statistical Analysis 1 for Determination of Best Overall Response Rate (BORR)
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0433
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).

Statistical Analysis 2 for Determination of Best Overall Response Rate (BORR)
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0012
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).

Statistical Analysis 3 for Determination of Best Overall Response Rate (BORR)
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0402
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).



9.  Secondary:   Time to Response   [ Time Frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) ]

Measure Type Secondary
Measure Title Time to Response
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Responder subjects in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  23     15     2  
Time to Response  
[units: months]
Mean ( Full Range )
  3.324  
  ( 2.10 to 5.59 )  
  3.176  
  ( 2.60 to 5.52 )  
  2.743  
  ( 2.69 to 2.79 )  

No statistical analysis provided for Time to Response



10.  Secondary:   Duration of Response   [ 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]) ]

Measure Type Secondary
Measure Title Duration of Response
Measure 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])  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  23     15     2  
Duration of Response  
[units: months]
Median ( 95% Confidence Interval )
  11.47  
  ( 5.36 to NA ) [1]
  NA  
  ( 28.09 to NA ) [2]
  NA  
  ( 2.00 to NA ) [3]
[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.

No statistical analysis provided for Duration of Response



11.  Secondary:   Disease Control Rate (DCR)   [ Time Frame: Up to week 24 ]

Measure Type Secondary
Measure Title Disease Control Rate (DCR)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  403     137     136  
Disease Control Rate (DCR)  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  20.1  
  ( 16.3 to 24.3 )  
  28.5  
  ( 21.1 to 36.8 )  
  11.0  
  ( 6.3 to 17.5 )  


Statistical Analysis 1 for Disease Control Rate (DCR)
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0179
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).

Statistical Analysis 2 for Disease Control Rate (DCR)
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).

Statistical Analysis 3 for Disease Control Rate (DCR)
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0429
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).



12.  Secondary:   Delayed Response (Response Beyond Week 24)   [ 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]) ]

Measure Type Secondary
Measure Title Delayed Response (Response Beyond Week 24)
Measure 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])  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  88     40     18  
Delayed Response (Response Beyond Week 24)  
[units: 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  

No statistical analysis provided for Delayed Response (Response Beyond Week 24)



13.  Secondary:   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   [ Time Frame: Baseline (Day 1, Cycle1), Week 12 ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  381     131     131  
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  
[units: units on a scale]
Least Squares Mean ( 95% Confidence Interval )
     
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 )  


Statistical Analysis 1 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.2805
Mean Difference (Final Values) [4] 3.0
95% Confidence Interval ( -2.5 to 8.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Global quality of life change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 2 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.6300
Mean Difference (Final Values) [4] 1.6
95% Confidence Interval ( -5.0 to 8.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Global quality of life change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 3 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.6026
Mean Difference (Final Values) [4] 1.4
95% Confidence Interval ( -3.9 to 6.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Global quality of life change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 4 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.1219
Mean Difference (Final Values) [4] 3.9
95% Confidence Interval ( -1.1 to 8.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Physical change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 5 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.0978
Mean Difference (Final Values) [4] 5.0
95% Confidence Interval ( -0.9 to 11.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Physical change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 6 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.6590
Mean Difference (Final Values) [4] -1.1
95% Confidence Interval ( -6.0 to 3.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Physical change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 7 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.2480
Mean Difference (Final Values) [4] 4.3
95% Confidence Interval ( -3.0 to 11.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Role change, change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 8 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.4742
Mean Difference (Final Values) [4] 3.2
95% Confidence Interval ( -5.6 to 12.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Role change, change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 9 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.7597
Mean Difference (Final Values) [4] 1.1
95% Confidence Interval ( -6.1 to 8.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Role change, change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 10 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.9119
Mean Difference (Final Values) [4] 0.3
95% Confidence Interval ( -4.7 to 5.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Cognitive change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 11 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.7616
Mean Difference (Final Values) [4] -0.9
95% Confidence Interval ( -6.9 to 5.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Cognitive change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 12 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.6266
Mean Difference (Final Values) [4] 1.2
95% Confidence Interval ( -3.6 to 6.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Cognitive change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 13 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.9984
Mean Difference (Final Values) [4] 0.0
95% Confidence Interval ( -4.8 to 4.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Emotional change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 14 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.4873
Mean Difference (Final Values) [4] -2.0
95% Confidence Interval ( -7.8 to 3.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Emotional change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 15 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.3938
Mean Difference (Final Values) [4] 2.0
95% Confidence Interval ( -2.7 to 6.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Emotional change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 16 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.6695
Mean Difference (Final Values) [4] -1.4
95% Confidence Interval ( -8.1 to 5.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Social change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 17 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.4041
Mean Difference (Final Values) [4] -3.4
95% Confidence Interval ( -11.3 to 4.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Social change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 18 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.5538
Mean Difference (Final Values) [4] 1.9
95% Confidence Interval ( -4.5 to 8.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Social change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 19 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.2259
Mean Difference (Final Values) [4] -3.9
95% Confidence Interval ( -10.3 to 2.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Fatigue change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 20 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.6168
Mean Difference (Final Values) [4] -2.0
95% Confidence Interval ( -9.6 to 5.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Fatigue change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 21 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.5329
Mean Difference (Final Values) [4] -2.0
95% Confidence Interval ( -8.2 to 4.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Fatigue change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 22 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.9397
Mean Difference (Final Values) [4] 0.2
95% Confidence Interval ( -4.7 to 5.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Nausea and Vomiting change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 23 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.6716
Mean Difference (Final Values) [4] -1.3
95% Confidence Interval ( -7.1 to 4.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Nausea and Vomiting change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 24 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.5497
Mean Difference (Final Values) [4] 1.4
95% Confidence Interval ( -3.3 to 6.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Nausea and Vomiting change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 25 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.0625
Mean Difference (Final Values) [4] -6.3
95% Confidence Interval ( -12.8 to 0.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Pain change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 26 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.3214
Mean Difference (Final Values) [4] -4.0
95% Confidence Interval ( -11.9 to 3.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Pain change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 27 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.4898
Mean Difference (Final Values) [4] -2.3
95% Confidence Interval ( -8.7 to 4.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Pain change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 28 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.0761
Mean Difference (Final Values) [4] -5.6
95% Confidence Interval ( -11.8 to 0.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Dyspnea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 29 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.3187
Mean Difference (Final Values) [4] -3.8
95% Confidence Interval ( -11.2 to 3.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Dyspnea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 30 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.5548
Mean Difference (Final Values) [4] -1.8
95% Confidence Interval ( -7.9 to 4.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Dyspnea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 31 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.2450
Mean Difference (Final Values) [4] -4.5
95% Confidence Interval ( -12.1 to 3.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Sleep disturbance change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 32 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.8464
Mean Difference (Final Values) [4] -0.9
95% Confidence Interval ( -10.0 to 8.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Sleep disturbance change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 33 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.3351
Mean Difference (Final Values) [4] -3.6
95% Confidence Interval ( -10.9 to 3.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Sleep Disturbance change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 34 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.6291
Mean Difference (Final Values) [4] -1.8
95% Confidence Interval ( -9.1 to 5.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Appetite loss change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 35 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.7675
Mean Difference (Final Values) [4] 1.3
95% Confidence Interval ( -7.4 to 10.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Appetite Loss change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 36 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.3911
Mean Difference (Final Values) [4] -3.1
95% Confidence Interval ( -10.2 to 4.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Appetite Loss change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 37 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.0431
Mean Difference (Final Values) [4] -6.5
95% Confidence Interval ( -12.9 to -0.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Constipation change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 38 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.0101
Mean Difference (Final Values) [4] -9.9
95% Confidence Interval ( -17.4 to -2.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Constipation change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 39 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.2796
Mean Difference (Final Values) [4] 3.4
95% Confidence Interval ( -2.8 to 9.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Constipation change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 40 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.1940
Mean Difference (Final Values) [4] 4.3
95% Confidence Interval ( -2.2 to 10.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Diarrhea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 41 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.0821
Mean Difference (Final Values) [4] 6.9
95% Confidence Interval ( -0.9 to 14.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Diarrhea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 42 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.4169
Mean Difference (Final Values) [4] -2.6
95% Confidence Interval ( -9.0 to 3.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Diarrhea change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 43 for 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
Groups [1] Ipilimumab Plus gp100 vs. gp100
Method [2] ANCOVA
P Value [3] 0.5717
Mean Difference (Final Values) [4] -1.7
95% Confidence Interval ( -7.5 to 4.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Financial Impact change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 44 for 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
Groups [1] Ipilimumab Monotherapy vs. gp100
Method [2] ANCOVA
P Value [3] 0.6949
Mean Difference (Final Values) [4] 1.4
95% Confidence Interval ( -5.6 to 8.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Financial Impact change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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.

Statistical Analysis 45 for 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
Groups [1] Ipilimumab Plus gp100 vs. Ipilimumab Monotherapy
Method [2] ANCOVA
P Value [3] 0.2849
Mean Difference (Final Values) [4] -3.1
95% Confidence Interval ( -8.8 to 2.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Financial Impact change from baseline
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death   [ 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]). ]

Measure Type Secondary
Measure Title Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Measure 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]).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects who received at least 1 dose or any partial dose of study medication.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death  
[units: 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  

No statistical analysis provided for Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death



15.  Secondary:   Percentage of Participants With Immune-Related Adverse Events (irAEs)   [ 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]). ]

Measure Type Secondary
Measure Title Percentage of Participants With Immune-Related Adverse Events (irAEs)
Measure 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]).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects who received at least 1 dose or any partial dose of study medication.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Percentage of Participants With Immune-Related Adverse Events (irAEs)  
[units: 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  

No statistical analysis provided for Percentage of Participants With Immune-Related Adverse Events (irAEs)



16.  Secondary:   Percentage of Participants With Worst On-Study Hematological Abnormalities   [ 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]). ]

Measure Type Secondary
Measure Title Percentage of Participants With Worst On-Study Hematological Abnormalities
Measure 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]).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Percentage of Participants With Worst On-Study Hematological Abnormalities  
[units: 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  

No statistical analysis provided for Percentage of Participants With Worst On-Study Hematological Abnormalities



17.  Secondary:   Percentage of Participants With Worst On-Study Liver Abnormalities   [ 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]). ]

Measure Type Secondary
Measure Title Percentage of Participants With Worst On-Study Liver Abnormalities
Measure 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]).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Percentage of Participants With Worst On-Study Liver Abnormalities  
[units: 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  

No statistical analysis provided for Percentage of Participants With Worst On-Study Liver Abnormalities



18.  Secondary:   Percentage of Participants With Worst On-Study Renal Abnormalities   [ 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]). ]

Measure Type Secondary
Measure Title Percentage of Participants With Worst On-Study Renal Abnormalities
Measure 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]).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Percentage of Participants With Worst On-Study Renal Abnormalities  
[units: 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  

No statistical analysis provided for Percentage of Participants With Worst On-Study Renal Abnormalities



19.  Secondary:   Clinically Meaningful Changes in Vital Signs and Physical Examinations   [ 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 ]

Measure Type Secondary
Measure Title Clinically Meaningful Changes in Vital Signs and Physical Examinations
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects who received at least 1 dose or any partial dose of study medication.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Measured Values
    Ipilimumab Plus gp100     Ipilimumab Monotherapy     gp100  
Number of Participants Analyzed  
[units: participants]
  380     131     132  
Clinically Meaningful Changes in Vital Signs and Physical Examinations  
[units: participants]
     
Clinically Meaningful Vital Sign Changes     0     0     0  
Clinically Meaningful Physical Examination Changes     0     0     0  

No statistical analysis provided for Clinically Meaningful Changes in Vital Signs and Physical Examinations




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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