Trial Outcomes & Findings for MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma (NCT NCT00094653)
NCT ID: NCT00094653
Last Updated: 2011-07-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1783 participants
Primary outcome timeframe
From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Results posted on
2011-07-11
Participant Flow
Of the 1783 participants who enrolled and were screened for study participation, a total of 676 subjects were randomized.
Participant milestones
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
403
|
137
|
136
|
|
Overall Study
Treated
|
381
|
131
|
131
|
|
Overall Study
COMPLETED
|
82
|
31
|
10
|
|
Overall Study
NOT COMPLETED
|
321
|
106
|
126
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
Death
|
306
|
100
|
119
|
|
Overall Study
Subject Withdrew Consent
|
10
|
2
|
3
|
|
Overall Study
Other
|
2
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
Baseline Characteristics
MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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
n=676 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
55.6 years
n=5 Participants
|
56.8 years
n=7 Participants
|
57.4 years
n=5 Participants
|
56.2 years
n=4 Participants
|
|
Age, Customized
< 65 years
|
291 participants
n=5 Participants
|
95 participants
n=7 Participants
|
94 participants
n=5 Participants
|
480 participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
112 participants
n=5 Participants
|
42 participants
n=7 Participants
|
42 participants
n=5 Participants
|
196 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
275 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
247 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
401 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
380 Participants
n=5 Participants
|
129 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
638 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
18 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Duration of Melanoma
|
5.09 years
n=5 Participants
|
4.34 years
n=7 Participants
|
5.65 years
n=5 Participants
|
5.05 years
n=4 Participants
|
|
Melanoma Stage
M0
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Melanoma Stage
M1a
|
37 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
62 Participants
n=4 Participants
|
|
Melanoma Stage
M1b
|
76 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
121 Participants
n=4 Participants
|
|
Melanoma Stage
M1c
|
285 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
483 Participants
n=4 Participants
|
|
Prior Interleukin-2 Therapy
No
|
314 Participants
n=5 Participants
|
105 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
522 Participants
n=4 Participants
|
|
Prior Interleukin-2 Therapy
Yes
|
89 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
154 Participants
n=4 Participants
|
|
Lactate Dehydrogenase
>upper limit of normal (ULN)
|
149 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
254 Participants
n=4 Participants
|
|
Lactate Dehydrogenase
<=ULN
|
252 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
417 Participants
n=4 Participants
|
|
Lactate Dehydrogenase
unknown
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
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
|
9.95 months
Interval 8.48 to 11.5
|
6.44 months
Interval 5.49 to 8.71
|
—
|
SECONDARY outcome
Timeframe: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288\[288V\]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217\[210M\]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
|
|---|---|---|---|
|
Overall 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
|
9.95 months
Interval 8.48 to 11.5
|
10.12 months
Interval 8.02 to 13.8
|
6.44 months
Interval 5.49 to 8.71
|
SECONDARY outcome
Timeframe: Month 12, Month 18, Month 24Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
12-, 18-, and 24-Month Survival Rates
18-Month Survival Rate
|
0.300 probability
Interval 0.254 to 0.347
|
0.332 probability
Interval 0.249 to 0.417
|
0.163 probability
Interval 0.101 to 0.23
|
|
12-, 18-, and 24-Month Survival Rates
24-Month Survival Rate
|
0.216 probability
Interval 0.172 to 0.261
|
0.235 probability
Interval 0.16 to 0.315
|
0.137 probability
Interval 0.08 to 0.2
|
|
12-, 18-, and 24-Month Survival Rates
12-Month Survival Rate
|
0.436 probability
Interval 0.386 to 0.485
|
0.456 probability
Interval 0.37 to 0.541
|
0.253 probability
Interval 0.181 to 0.329
|
SECONDARY outcome
Timeframe: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)Population: 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.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Progression Free Survival (PFS)
|
2.76 months
Interval 2.73 to 2.79
|
2.86 months
Interval 2.76 to 3.02
|
2.76 months
Interval 2.73 to 2.83
|
SECONDARY outcome
Timeframe: Week 12, Week 24Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
Week 12
|
0.491 percentage of participants
Interval 0.441 to 0.539
|
0.577 percentage of participants
Interval 0.489 to 0.655
|
0.485 percentage of participants
Interval 0.396 to 0.567
|
|
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
Week 24
|
0.164 percentage of participants
Interval 0.129 to 0.203
|
0.240 percentage of participants
Interval 0.171 to 0.315
|
0.100 percentage of participants
Interval 0.056 to 0.159
|
SECONDARY outcome
Timeframe: 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])Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Time to Progression (TTP)
|
2.76 months
Interval 2.73 to 2.79
|
2.86 months
Interval 2.76 to 3.02
|
2.76 months
Interval 2.73 to 2.83
|
SECONDARY outcome
Timeframe: BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Complete Response
|
1 participants
|
2 participants
|
0 participants
|
|
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Partial Response
|
22 participants
|
13 participants
|
2 participants
|
|
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Stable Disease
|
58 participants
|
24 participants
|
13 participants
|
|
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Progressed Disease
|
239 participants
|
70 participants
|
89 participants
|
|
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Not Evaluated, Missing, or Unknown
|
83 participants
|
28 participants
|
32 participants
|
SECONDARY outcome
Timeframe: Up to week 24Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Determination of Best Overall Response Rate (BORR)
|
5.7 percentage of participants
Interval 3.7 to 8.4
|
10.9 percentage of participants
Interval 6.3 to 17.4
|
1.5 percentage of participants
Interval 0.2 to 5.2
|
SECONDARY outcome
Timeframe: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)Population: Responder subjects in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=23 Participants
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
n=15 Participants
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
n=2 Participants
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.
|
|---|---|---|---|
|
Time to Response
|
3.324 months
Full Range 0.9561 • Interval 2.1 to 5.59
|
3.176 months
Full Range 0.7629 • Interval 2.6 to 5.52
|
2.743 months
Full Range 0.0697 • Interval 2.69 to 2.79
|
SECONDARY outcome
Timeframe: 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])Population: 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.
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).
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=23 Participants
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
n=15 Participants
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
n=2 Participants
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.
|
|---|---|---|---|
|
Duration of Response
|
11.47 months
Interval 5.36 to
Upper limit of 95% CI was not reached because most subjects were censored and the upper bound was not estimable.
|
NA months
Interval 28.09 to
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).
|
NA months
Interval 2.0 to
The limited number of responses (2) in the gp100 monotherapy group prevented a median duration from being reached.
|
SECONDARY outcome
Timeframe: Up to week 24Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=403 Participants
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
n=137 Participants
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
n=136 Participants
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.
|
|---|---|---|---|
|
Disease Control Rate (DCR)
|
20.1 percentage of participants
Interval 16.3 to 24.3
|
28.5 percentage of participants
Interval 21.1 to 36.8
|
11.0 percentage of participants
Interval 6.3 to 17.5
|
SECONDARY outcome
Timeframe: 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])Population: 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).
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=88 Participants
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
n=40 Participants
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
n=18 Participants
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.
|
|---|---|---|---|
|
Delayed Response (Response Beyond Week 24)
Complete Response Beyond Week 24
|
1 participants
|
3 participants
|
0 participants
|
|
Delayed Response (Response Beyond Week 24)
Partial Response Beyond Week 24
|
3 participants
|
2 participants
|
0 participants
|
|
Delayed Response (Response Beyond Week 24)
Stable Disease Beyond Week 24
|
3 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Cycle1), Week 12Population: 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.
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).
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=381 Participants
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
n=131 Participants
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
n=131 Participants
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.
|
|---|---|---|---|
|
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
Global QOL (n=226, 83, 77)
|
-7.4 units on a scale
Interval -10.4 to -4.3
|
-8.8 units on a scale
Interval -13.5 to -4.1
|
-10.4 units on a scale
Interval -15.3 to -5.5
|
|
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
Physical (n=226 83, 78)
|
-6.2 units on a scale
Interval -8.9 to -3.4
|
-5.1 units on a scale
Interval -9.4 to -0.8
|
-10.1 units on a scale
Interval -14.5 to -5.7
|
|
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
Role Change (n=226, 83, 78)
|
-9.3 units on a scale
Interval -13.4 to -5.3
|
-10.5 units on a scale
Interval -16.8 to -4.1
|
-13.7 units on a scale
Interval -20.2 to -7.2
|
|
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
Emotional (n=227, 83, 78)
|
-1.5 units on a scale
Interval -4.2 to 1.1
|
-3.6 units on a scale
Interval -7.7 to 0.6
|
-1.5 units on a scale
Interval -5.8 to 2.7
|
|
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
Social (n=227, 83, 76)
|
-5.6 units on a scale
Interval -9.2 to -2.0
|
-7.5 units on a scale
Interval -13.2 to -1.9
|
-4.2 units on a scale
Interval -10.1 to 1.8
|
|
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
Nausea and Vomiting (n=226, 83, 78)
|
4.6 units on a scale
Interval 1.9 to 7.3
|
3.1 units on a scale
Interval -1.0 to 7.3
|
4.4 units on a scale
Interval 0.1 to 8.7
|
|
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
Dyspnea (n=222, 81, 77)
|
3.5 units on a scale
Interval 0.0 to 6.9
|
5.3 units on a scale
Interval -0.1 to 10.7
|
9.1 units on a scale
Interval 3.6 to 14.6
|
|
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
Cognitive (n=226, 83, 78)
|
-3.1 units on a scale
Interval -5.8 to -0.3
|
-4.3 units on a scale
Interval -8.6 to 0.0
|
-3.4 units on a scale
Interval -7.8 to 1.0
|
|
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
Fatigue (n=226, 82, 78)
|
10.6 units on a scale
Interval 7.0 to 14.1
|
12.5 units on a scale
Interval 7.0 to 18.1
|
14.5 units on a scale
Interval 8.8 to 20.2
|
|
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
Pain (n=227, 83, 78)
|
5.6 units on a scale
Interval 2.0 to 9.3
|
7.9 units on a scale
Interval 2.2 to 13.6
|
11.9 units on a scale
Interval 6.0 to 17.7
|
|
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
Sleep Disturbance (n=225, 83, 76)
|
6.5 units on a scale
Interval 2.3 to 10.7
|
10.1 units on a scale
Interval 3.6 to 16.6
|
11.0 units on a scale
Interval 4.3 to 17.8
|
|
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
Appetite Loss (n=225, 83, 78)
|
8.5 units on a scale
Interval 4.4 to 12.5
|
11.6 units on a scale
Interval 5.3 to 17.9
|
10.3 units on a scale
Interval 3.8 to 16.8
|
|
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
Constipation (n=225, 83, 77)
|
5.2 units on a scale
Interval 1.7 to 8.7
|
1.9 units on a scale
Interval -3.5 to 7.2
|
11.8 units on a scale
Interval 6.2 to 17.4
|
|
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
Diarrhea (n=223, 82, 78)
|
6.4 units on a scale
Interval 2.8 to 10.1
|
9.1 units on a scale
Interval 3.4 to 14.7
|
2.1 units on a scale
Interval -3.7 to 7.9
|
|
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
Financial Impact (n=226, 83, 76)
|
0.0 units on a scale
Interval -3.2 to 3.2
|
3.1 units on a scale
Interval -1.9 to 8.1
|
1.7 units on a scale
Interval -3.5 to 6.9
|
SECONDARY outcome
Timeframe: 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]).Population: All subjects who received at least 1 dose or any partial dose of study medication.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
On-Study AEs Leading to Discontinuation
|
9.2 percentage of participants
|
13.0 percentage of participants
|
3.8 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
AEs with Outcome of Death
|
6.1 percentage of participants
|
9.9 percentage of participants
|
6.1 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Any On-Study AE
|
98.4 percentage of participants
|
96.9 percentage of participants
|
97.0 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Severe (>=Grade 3) On-Study AEs
|
50.8 percentage of participants
|
55.0 percentage of participants
|
52.3 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Serious On-Study AEs
|
40.8 percentage of participants
|
42.0 percentage of participants
|
39.4 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Related On-Study AEs
|
88.9 percentage of participants
|
80.2 percentage of participants
|
78.8 percentage of participants
|
|
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Related AE with Outcome of Death
|
2.1 percentage of participants
|
3.1 percentage of participants
|
1.5 percentage of participants
|
SECONDARY outcome
Timeframe: 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]).Population: All subjects who received at least 1 dose or any partial dose of study medication.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Any On-Study irAEs
|
58.2 percentage of participants
|
61.1 percentage of participants
|
31.8 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
On-Study Severe irAEs
|
11.3 percentage of participants
|
15.3 percentage of participants
|
3.0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
On-Study Serious irAEs
|
10.5 percentage of participants
|
13.0 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
On-Study irAEs Leading to Discontinuation
|
5.8 percentage of participants
|
8.4 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Death Due to irAEs
|
1.3 percentage of participants
|
1.5 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Gastrointestinal irAEs (any grade)
|
32.1 percentage of participants
|
29.0 percentage of participants
|
14.4 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Liver irAEs (any grade)
|
2.1 percentage of participants
|
3.8 percentage of participants
|
4.5 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Liver irAEs
|
1.1 percentage of participants
|
0.8 percentage of participants
|
2.3 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Endocrine irAEs (any grade)
|
3.9 percentage of participants
|
7.6 percentage of participants
|
1.5 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Endocrine irAEs
|
1.1 percentage of participants
|
3.8 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Skin irAEs (any grade)
|
40.0 percentage of participants
|
43.5 percentage of participants
|
16.7 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Skin irAEs
|
2.4 percentage of participants
|
1.5 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Neurological irAEs (any grade)
|
0.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Neurological irAEs
|
0.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Other irAEs (any grade)
|
3.2 percentage of participants
|
4.6 percentage of participants
|
2.3 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Other irAEs
|
1.6 percentage of participants
|
2.3 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Severe (>= Grade 3) Gastrointestinal irAEs
|
6.3 percentage of participants
|
7.6 percentage of participants
|
0.8 percentage of participants
|
SECONDARY outcome
Timeframe: 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]).Population: 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.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 0 (n=352, 121, 126)
|
97.2 percentage of participants
|
95.9 percentage of participants
|
92.9 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 1 (n=352, 121, 126)
|
1.4 percentage of participants
|
1.7 percentage of participants
|
5.6 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 3 (n=352, 121, 126)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 4 (n=352, 121, 126)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 1-4 (n=352, 121, 126)
|
2.8 percentage of participants
|
4.1 percentage of participants
|
7.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 3 (n=352, 121, 126)
|
0.6 percentage of participants
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 4 (n=352, 121, 126)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 1-4 (n=352, 121, 126)
|
4.5 percentage of participants
|
6.6 percentage of participants
|
4.0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 3-4 (n=352, 121, 126)
|
0.9 percentage of participants
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 0 (n=349, 121, 126)
|
94.6 percentage of participants
|
90.1 percentage of participants
|
91.3 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 1 (n=349, 121, 126)
|
4.9 percentage of participants
|
9.1 percentage of participants
|
8.7 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 3-4 (n=349, 121, 126)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 0 (n=352, 121, 126)
|
33.8 percentage of participants
|
34.7 percentage of participants
|
22.2 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 1 (n=352, 121, 126)
|
46.3 percentage of participants
|
47.9 percentage of participants
|
42.9 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 2 (n=352, 121, 126)
|
15.1 percentage of participants
|
14.9 percentage of participants
|
25.4 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 3 (n=352, 121, 126)
|
4.3 percentage of participants
|
2.5 percentage of participants
|
9.5 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 0 (n=352, 121, 126)
|
48.9 percentage of participants
|
44.6 percentage of participants
|
46.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 1 (n=352, 121, 126)
|
37.2 percentage of participants
|
40.5 percentage of participants
|
34.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 2 (n=352, 121, 126)
|
12.2 percentage of participants
|
14.0 percentage of participants
|
15.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 3 (n=352, 121, 126)
|
1.7 percentage of participants
|
0.8 percentage of participants
|
4.0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 4 (n=352, 121, 126)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 1-4 (n=352, 121, 126)
|
51.1 percentage of participants
|
55.4 percentage of participants
|
53.2 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Hemoglobin, Grade 3-4 (n=352, 121, 126)
|
1.7 percentage of participants
|
0.8 percentage of participants
|
4.0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 2 (n=352, 121, 126)
|
1.1 percentage of participants
|
2.5 percentage of participants
|
1.6 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
White Blood Cells, Grade 3-4 (n=352, 121, 126)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 0 (n=352, 121, 126)
|
95.5 percentage of participants
|
93.4 percentage of participants
|
96.0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 1 (n=352, 121, 126)
|
2.8 percentage of participants
|
3.3 percentage of participants
|
2.4 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
ANC, Grade 2 (n=352, 121, 126)
|
0.9 percentage of participants
|
2.5 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 2 (n=349, 121, 126)
|
0.6 percentage of participants
|
0.8 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 3 (n=349, 121, 126)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 4 (n=349, 121, 126)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Platelet Count, Grade 1-4 (n=349, 121, 126)
|
5.4 percentage of participants
|
9.9 percentage of participants
|
8.7 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 4 (n=352, 121, 126)
|
0.6 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 1-4(n=352, 121, 126)
|
66.2 percentage of participants
|
65.3 percentage of participants
|
77.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Hematological Abnormalities
Lymphocytes (absolute), Grade 3-4(n=352, 121, 126)
|
4.8 percentage of participants
|
2.5 percentage of participants
|
9.5 percentage of participants
|
SECONDARY outcome
Timeframe: 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]).Population: 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.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 4 (n=352, 121, 126)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 1-4 (n=352, 121, 126)
|
16.8 percentage of participants
|
24.0 percentage of participants
|
15.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 0 (n=352, 121, 126)
|
80.4 percentage of participants
|
71.9 percentage of participants
|
81.7 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 1 (n=352, 121, 126)
|
16.5 percentage of participants
|
23.1 percentage of participants
|
15.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 2 (n=352, 121, 126)
|
1.4 percentage of participants
|
3.3 percentage of participants
|
2.4 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 3 (n=352, 121, 126)
|
1.4 percentage of participants
|
1.7 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 2 (n=353, 121, 127)
|
1.4 percentage of participants
|
1.7 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 3 (n=353, 121, 127)
|
0.6 percentage of participants
|
0.8 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 4 (n=353, 121, 127)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 1-4 (n=353, 121, 127)
|
4.5 percentage of participants
|
6.6 percentage of participants
|
1.6 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 3-4 (n=353, 121, 127)
|
0.6 percentage of participants
|
0.8 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 0 (n=353, 121, 128)
|
73.7 percentage of participants
|
71.9 percentage of participants
|
71.1 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 1 (n=353, 121, 128)
|
19.8 percentage of participants
|
20.7 percentage of participants
|
24.2 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 2 (n=353, 121, 128)
|
4.8 percentage of participants
|
4.1 percentage of participants
|
3.9 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 4 (n=352, 121, 126)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 1-4 (n=352, 121, 126)
|
19.6 percentage of participants
|
28.1 percentage of participants
|
18.3 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
AST, Grade 3-4 (n=352, 121, 126)
|
1.7 percentage of participants
|
1.7 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 0 (n=353, 121, 127)
|
95.5 percentage of participants
|
93.4 percentage of participants
|
98.4 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Total Bilirubin, Grade 1 (n=353, 121, 127)
|
2.5 percentage of participants
|
4.1 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 3 (n=353, 121, 128)
|
1.7 percentage of participants
|
3.3 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 4 (n=353, 121, 128)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 1-4 (n=353, 121, 128)
|
26.3 percentage of participants
|
28.1 percentage of participants
|
28.9 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
Alkaline Phosphatase, Grade 3-4 (n=353, 121, 128)
|
1.7 percentage of participants
|
3.3 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 0 (n=352, 121, 126)
|
83.2 percentage of participants
|
76.0 percentage of participants
|
84.9 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 1 (n=352, 121, 126)
|
13.6 percentage of participants
|
19.0 percentage of participants
|
12.7 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 2 (n=352, 121, 126)
|
2.0 percentage of participants
|
3.3 percentage of participants
|
1.6 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 3 (n=352, 121, 126)
|
0.9 percentage of participants
|
1.7 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Worst On-Study Liver Abnormalities
ALT, Grade 3-4 (n=352, 121, 126)
|
1.1 percentage of participants
|
1.7 percentage of participants
|
0.8 percentage of participants
|
SECONDARY outcome
Timeframe: 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]).Population: 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.
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.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 4 (n=353, 121, 128)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 1-4 (n=353, 121, 128)
|
10.5 percentage of participants
|
11.6 percentage of participants
|
11.7 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 3-4 (n=353, 121, 128)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 0 (n=353, 121, 128)
|
89.5 percentage of participants
|
88.4 percentage of participants
|
88.3 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 1 (n=353, 121, 128)
|
8.8 percentage of participants
|
9.9 percentage of participants
|
9.4 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 2 (n=353, 121, 128)
|
1.4 percentage of participants
|
1.7 percentage of participants
|
2.3 percentage of participants
|
|
Percentage of Participants With Worst On-Study Renal Abnormalities
Creatinine, Grade 3 (n=353, 121, 128)
|
0.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 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 thereafterPopulation: All subjects who received at least 1 dose or any partial dose of study medication.
Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.
Outcome measures
| Measure |
Ipilimumab Plus gp100
n=380 Participants
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
n=131 Participants
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
n=132 Participants
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.
|
|---|---|---|---|
|
Clinically Meaningful Changes in Vital Signs and Physical Examinations
Clinically Meaningful Vital Sign Changes
|
0 participants
|
0 participants
|
0 participants
|
|
Clinically Meaningful Changes in Vital Signs and Physical Examinations
Clinically Meaningful Physical Examination Changes
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Ipilimumab Monotherapy
Serious events: 55 serious events
Other events: 124 other events
Deaths: 0 deaths
Ipilimumab Plus gp100
Serious events: 155 serious events
Other events: 362 other events
Deaths: 0 deaths
gp100
Serious events: 52 serious events
Other events: 124 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ipilimumab Monotherapy
n=131 participants at risk
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
|
Ipilimumab Plus gp100
n=380 participants at risk
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
n=132 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
1.5%
2/131
|
1.1%
4/380
|
3.8%
5/132
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
ABDOMINAL WALL MASS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
ACUTE HEPATIC FAILURE
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
ADVERSE EVENT
|
0.76%
1/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Blood and lymphatic system disorders
ANAEMIA
|
3.1%
4/131
|
1.3%
5/380
|
3.8%
5/132
|
|
Vascular disorders
ANGIOPATHY
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Nervous system disorders
APHASIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Vascular disorders
ARTERIAL THROMBOSIS LIMB
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
ASCITES
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
General disorders
ASTHENIA
|
2.3%
3/131
|
1.1%
4/380
|
0.76%
1/132
|
|
Nervous system disorders
ATAXIA
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Renal and urinary disorders
ATONIC URINARY BLADDER
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/131
|
0.53%
2/380
|
1.5%
2/132
|
|
Infections and infestations
BACTERAEMIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
BILE DUCT OBSTRUCTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Renal and urinary disorders
BLADDER PAIN
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Investigations
BLOOD CORTICOTROPHIN DECREASED
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Nervous system disorders
BRAIN OEDEMA
|
0.76%
1/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Reproductive system and breast disorders
BREAST MASS
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHIAL OBSTRUCTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
BRONCHOPNEUMONIA
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
CARDIAC TAMPONADE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
CARDIOPULMONARY FAILURE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
CATHETER RELATED INFECTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.00%
0/131
|
0.00%
0/380
|
1.5%
2/132
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
CHEST PAIN
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
General disorders
CHILLS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
COLITIS
|
5.3%
7/131
|
3.7%
14/380
|
0.00%
0/132
|
|
Nervous system disorders
COMA
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
1.5%
2/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/131
|
0.79%
3/380
|
0.76%
1/132
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Infections and infestations
CYSTITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
1.5%
2/131
|
0.79%
3/380
|
0.76%
1/132
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
1.5%
2/131
|
1.3%
5/380
|
0.76%
1/132
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.76%
1/131
|
2.1%
8/380
|
3.0%
4/132
|
|
Psychiatric disorders
DELIRIUM
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
DIARRHOEA
|
4.6%
6/131
|
4.2%
16/380
|
0.00%
0/132
|
|
General disorders
DISEASE PROGRESSION
|
1.5%
2/131
|
1.6%
6/380
|
2.3%
3/132
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/131
|
0.00%
0/380
|
1.5%
2/132
|
|
Nervous system disorders
DYSARTHRIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.76%
1/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
2.3%
3/131
|
0.53%
2/380
|
5.3%
7/132
|
|
Infections and infestations
ENTEROCOCCAL BACTERAEMIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Nervous system disorders
EPIDURITIS
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Infections and infestations
ERYSIPELAS
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Infections and infestations
EYELID INFECTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
FAILURE TO THRIVE
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
General disorders
FATIGUE
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
General disorders
GAIT DISTURBANCE
|
0.76%
1/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Infections and infestations
GASTROINTESTINAL INFECTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
GASTROINTESTINAL PERFORATION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Injury, poisoning and procedural complications
GASTROINTESTINAL STOMA COMPLICATION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
0.00%
0/131
|
0.53%
2/380
|
1.5%
2/132
|
|
General disorders
GENERALISED OEDEMA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Renal and urinary disorders
GLOMERULONEPHRITIS
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Nervous system disorders
GUILLAIN-BARRE SYNDROME
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Vascular disorders
HAEMATOMA
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Blood and lymphatic system disorders
HAEMOLYTIC ANAEMIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Nervous system disorders
HAEMORRHAGE INTRACRANIAL
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOTHORAX
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/131
|
0.53%
2/380
|
0.76%
1/132
|
|
Hepatobiliary disorders
HEPATIC FAILURE
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
HEPATITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
HEPATITIS A
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Infections and infestations
HEPATITIS B
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
General disorders
HERNIA OBSTRUCTIVE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Nervous system disorders
HYDROCEPHALUS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Renal and urinary disorders
HYDRONEPHROSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Nervous system disorders
HYPOAESTHESIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Endocrine disorders
HYPOGONADISM
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
HYPOPHAGIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Endocrine disorders
HYPOPHYSITIS
|
1.5%
2/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Endocrine disorders
HYPOPITUITARISM
|
1.5%
2/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Vascular disorders
HYPOTENSION
|
2.3%
3/131
|
0.26%
1/380
|
1.5%
2/132
|
|
Endocrine disorders
HYPOTHYROIDISM
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
ILEUS
|
0.00%
0/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Infections and infestations
INFECTION
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
General disorders
INFUSION RELATED REACTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
INJECTION SITE REACTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
INJECTION SITE ULCER
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Investigations
INTERNATIONAL NORMALISED RATIO ABNORMAL
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
INTESTINAL HAEMORRHAGE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
INTESTINAL PERFORATION
|
0.00%
0/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Nervous system disorders
INTRACRANIAL PRESSURE INCREASED
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INTRACRANIAL TUMOUR HAEMORRHAGE
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
INTUSSUSCEPTION
|
0.00%
0/131
|
0.00%
0/380
|
1.5%
2/132
|
|
Eye disorders
IRIDOCYCLITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
JAUNDICE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Hepatobiliary disorders
JAUNDICE CHOLESTATIC
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
LARGE INTESTINAL OBSTRUCTION
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
LARGE INTESTINE PERFORATION
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Nervous system disorders
LETHARGY
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Skin and subcutaneous tissue disorders
LEUKOCYTOCLASTIC VASCULITIS
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
LOCALISED INFECTION
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Vascular disorders
LYMPHOEDEMA
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT ASCITES
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA
|
0.00%
0/131
|
0.79%
3/380
|
0.76%
1/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
0.00%
0/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Metabolism and nutrition disorders
MALNUTRITION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Nervous system disorders
MENINGEAL DISORDER
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Infections and infestations
MENINGITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO BREAST
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM
|
1.5%
2/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO SPINE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC MALIGNANT MELANOMA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC NEOPLASM
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC PAIN
|
0.76%
1/131
|
0.79%
3/380
|
0.00%
0/132
|
|
General disorders
MULTI-ORGAN FAILURE
|
0.00%
0/131
|
0.53%
2/380
|
1.5%
2/132
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Nervous system disorders
MYOCLONUS
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
NAUSEA
|
1.5%
2/131
|
1.6%
6/380
|
3.0%
4/132
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
OEDEMA
|
1.5%
2/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
OEDEMA PERIPHERAL
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
PAIN
|
0.76%
1/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/131
|
0.79%
3/380
|
0.76%
1/132
|
|
Respiratory, thoracic and mediastinal disorders
PAINFUL RESPIRATION
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
PATHOLOGICAL FRACTURE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Reproductive system and breast disorders
PELVIC PAIN
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
PERIRECTAL ABSCESS
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
PERITONITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
1.5%
2/131
|
1.3%
5/380
|
3.0%
4/132
|
|
Respiratory, thoracic and mediastinal disorders
PLEURITIC PAIN
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
PNEUMONIA
|
1.5%
2/131
|
2.1%
8/380
|
2.3%
3/132
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Musculoskeletal and connective tissue disorders
POLYMYALGIA RHEUMATICA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Injury, poisoning and procedural complications
PROCEDURAL COMPLICATION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
PROCTALGIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Infections and infestations
PSEUDOMONAL SEPSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.76%
1/131
|
0.79%
3/380
|
1.5%
2/132
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HAEMORRHAGE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
General disorders
PYREXIA
|
1.5%
2/131
|
1.8%
7/380
|
0.76%
1/132
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Skin and subcutaneous tissue disorders
RASH GENERALISED
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Skin and subcutaneous tissue disorders
RASH PRURITIC
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
RECTAL STENOSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Renal and urinary disorders
RENAL FAILURE
|
2.3%
3/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Renal and urinary disorders
RENAL TUBULAR NECROSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY ARREST
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY DEPRESSION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.76%
1/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Infections and infestations
SEPSIS
|
2.3%
3/131
|
1.1%
4/380
|
0.00%
0/132
|
|
Infections and infestations
SEPTIC SHOCK
|
0.76%
1/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.00%
0/131
|
0.00%
0/380
|
0.76%
1/132
|
|
Nervous system disorders
SPINAL CORD COMPRESSION
|
0.76%
1/131
|
0.79%
3/380
|
0.00%
0/132
|
|
Vascular disorders
SUPERIOR VENA CAVAL OCCLUSION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Nervous system disorders
SYNCOPE
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Cardiac disorders
TACHYCARDIA
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Vascular disorders
THROMBOSIS
|
0.76%
1/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Skin and subcutaneous tissue disorders
TOXIC EPIDERMAL NECROLYSIS
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR HAEMORRHAGE
|
0.00%
0/131
|
0.26%
1/380
|
1.5%
2/132
|
|
Metabolism and nutrition disorders
TUMOUR LYSIS SYNDROME
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN
|
1.5%
2/131
|
0.53%
2/380
|
0.76%
1/132
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Renal and urinary disorders
URETERIC OBSTRUCTION
|
0.00%
0/131
|
0.26%
1/380
|
0.00%
0/132
|
|
Renal and urinary disorders
URINARY INCONTINENCE
|
0.00%
0/131
|
0.26%
1/380
|
0.76%
1/132
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.00%
0/131
|
0.53%
2/380
|
0.00%
0/132
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/131
|
0.53%
2/380
|
2.3%
3/132
|
|
Investigations
URINE OUTPUT DECREASED
|
0.76%
1/131
|
0.00%
0/380
|
0.00%
0/132
|
|
Gastrointestinal disorders
VOMITING
|
2.3%
3/131
|
1.8%
7/380
|
2.3%
3/132
|
Other adverse events
| Measure |
Ipilimumab Monotherapy
n=131 participants at risk
Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
|
Ipilimumab Plus gp100
n=380 participants at risk
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
n=132 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/131
|
3.4%
13/380
|
6.8%
9/132
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
15.3%
20/131
|
16.8%
64/380
|
13.6%
18/132
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
5.3%
7/131
|
4.5%
17/380
|
8.3%
11/132
|
|
General disorders
ADVERSE EVENT
|
3.1%
4/131
|
5.8%
22/380
|
3.8%
5/132
|
|
Blood and lymphatic system disorders
ANAEMIA
|
10.7%
14/131
|
9.5%
36/380
|
16.7%
22/132
|
|
Psychiatric disorders
ANXIETY
|
3.8%
5/131
|
8.2%
31/380
|
6.8%
9/132
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
9.2%
12/131
|
7.9%
30/380
|
10.6%
14/132
|
|
General disorders
ASTHENIA
|
4.6%
6/131
|
9.7%
37/380
|
12.9%
17/132
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
6.9%
9/131
|
8.4%
32/380
|
12.1%
16/132
|
|
General disorders
CHILLS
|
6.9%
9/131
|
6.1%
23/380
|
5.3%
7/132
|
|
Gastrointestinal disorders
CONSTIPATION
|
20.6%
27/131
|
20.8%
79/380
|
25.8%
34/132
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
16.0%
21/131
|
14.5%
55/380
|
12.9%
17/132
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
25.2%
33/131
|
22.4%
85/380
|
22.0%
29/132
|
|
Gastrointestinal disorders
DIARRHOEA
|
31.3%
41/131
|
37.4%
142/380
|
19.7%
26/132
|
|
Nervous system disorders
DIZZINESS
|
3.8%
5/131
|
7.1%
27/380
|
9.8%
13/132
|
|
Gastrointestinal disorders
DYSPEPSIA
|
1.5%
2/131
|
3.7%
14/380
|
7.6%
10/132
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
12.2%
16/131
|
11.8%
45/380
|
15.2%
20/132
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
7.6%
10/131
|
6.8%
26/380
|
5.3%
7/132
|
|
General disorders
FATIGUE
|
42.0%
55/131
|
36.1%
137/380
|
31.1%
41/132
|
|
Gastrointestinal disorders
FLATULENCE
|
2.3%
3/131
|
2.4%
9/380
|
6.1%
8/132
|
|
Nervous system disorders
HEADACHE
|
14.5%
19/131
|
16.8%
64/380
|
13.6%
18/132
|
|
Vascular disorders
HOT FLUSH
|
4.6%
6/131
|
2.1%
8/380
|
6.1%
8/132
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
4.6%
6/131
|
3.7%
14/380
|
9.1%
12/132
|
|
Vascular disorders
HYPOTENSION
|
6.1%
8/131
|
3.2%
12/380
|
3.0%
4/132
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
5.3%
7/131
|
5.3%
20/380
|
2.3%
3/132
|
|
General disorders
INJECTION SITE ERYTHEMA
|
0.76%
1/131
|
6.8%
26/380
|
3.8%
5/132
|
|
General disorders
INJECTION SITE INDURATION
|
0.00%
0/131
|
6.6%
25/380
|
3.0%
4/132
|
|
General disorders
INJECTION SITE PAIN
|
1.5%
2/131
|
6.6%
25/380
|
9.8%
13/132
|
|
General disorders
INJECTION SITE REACTION
|
1.5%
2/131
|
28.7%
109/380
|
19.7%
26/132
|
|
Psychiatric disorders
INSOMNIA
|
12.2%
16/131
|
8.7%
33/380
|
11.4%
15/132
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
5.3%
7/131
|
1.8%
7/380
|
1.5%
2/132
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
3.8%
5/131
|
7.9%
30/380
|
7.6%
10/132
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
6.1%
8/131
|
7.4%
28/380
|
3.0%
4/132
|
|
Gastrointestinal disorders
NAUSEA
|
33.6%
44/131
|
33.4%
127/380
|
37.1%
49/132
|
|
General disorders
OEDEMA PERIPHERAL
|
9.2%
12/131
|
12.4%
47/380
|
16.7%
22/132
|
|
General disorders
PAIN
|
4.6%
6/131
|
6.1%
23/380
|
11.4%
15/132
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
6.9%
9/131
|
13.4%
51/380
|
14.4%
19/132
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
29.8%
39/131
|
20.8%
79/380
|
10.6%
14/132
|
|
General disorders
PYREXIA
|
11.5%
15/131
|
19.5%
74/380
|
17.4%
23/132
|
|
Skin and subcutaneous tissue disorders
RASH
|
22.1%
29/131
|
20.5%
78/380
|
6.8%
9/132
|
|
Infections and infestations
URINARY TRACT INFECTION
|
6.1%
8/131
|
2.1%
8/380
|
3.0%
4/132
|
|
Gastrointestinal disorders
VOMITING
|
22.9%
30/131
|
18.7%
71/380
|
20.5%
27/132
|
|
Investigations
WEIGHT DECREASED
|
6.1%
8/131
|
8.7%
33/380
|
9.1%
12/132
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER