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

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
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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
  Show 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) ]

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) ]

3.  Secondary:   12-, 18-, and 24-Month Survival Rates   [ Time Frame: Month 12, Month 18, Month 24 ]

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) ]

5.  Secondary:   Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24   [ Time Frame: Week 12, 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]) ]

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. ]

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

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) ]

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]) ]

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

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]) ]

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 ]
  Hide Outcome Measure 13

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]). ]

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]). ]

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]). ]

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]). ]

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]). ]

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 ]


  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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