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CompletedNCT00094653Updated Jul 11, 2011Results posted

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

A Phase 3 interventional study of MDX-010 (anti-CTLA4) monoclonal antibody and MDX-1379 (gp100) Melanoma Peptide Vaccine in Melanoma and Metastases, sponsored by Bristol-Myers Squibb. Completed at 209 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2011-07-11.

Sponsored by Bristol-Myers Squibb · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,783
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response [PR/CR]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.

Read the detailed description

Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.

02

Conditions studied

  • Melanoma
  • Metastases

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Keywords

  • melanoma
  • metastatic melanoma
  • skin cancer
03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 519 are open to participants now.

This study's enrollment of 1,783 is above the median of 38 across 2,350 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.

Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosed with malignant melanoma
  • Measurable unresectable Stage III or IV melanoma
  • HLA-A*0201 positive
  • Previous treatment with \& failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
  • At least 4 weeks since prior treatment
  • Negative pregnancy
  • Life expectancy greater than 4 months
  • Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
  • Required lab values
  • Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative

Exclusion criteria

Exclusion Criteria:

  • Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
  • Ocular melanoma
  • Active, untreated central nervous system (CNS) metastasis
  • Prior treatment with MDX-010 (anti-CTLA4) antibody
  • Prior treatment with any cancer therapeutic vaccine
  • Active autoimmune disease or history of autoimmune disease
  • Pregnancy or nursing
  • Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
  • Underlying medical conditions deemed hazardous if treated with study drug
  • Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
  • Unable to provide informed consent
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
1,783 participants (actual)

Study arms

  • Active comparator
    1

    Melanoma Peptide Vaccine (MDX-1379) (gp100) + Placebo

    Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine

  • Experimental
    2

    MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine)

    Drug: MDX-010 (anti-CTLA4) monoclonal antibody · Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine

  • Active comparator
    3

    MDX-010 (ipilimumab) + Placebo

    Drug: MDX-010 (anti-CTLA4) monoclonal antibody

Interventions

  • DrugMDX-010 (anti-CTLA4) monoclonal antibody

    3mg/kg (intravenous \[iv\] infusion over 90 minutes), every 3 weeks for 4 doses

    Also known as: ipilimumab

  • BiologicalMDX-1379 (gp100) Melanoma Peptide Vaccine

    2mL (2 subcutaneous injections of 2 mL each, 1 to each thigh), every 3 weeks for 4 doses.

    Also known as: melanoma peptide vaccine

06

What researchers measure

Primary outcomes

  1. 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

    OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    Time frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

Secondary outcomes

  1. 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

    OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    Time frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

  2. 12-, 18-, and 24-Month Survival Rates

    The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.

    Time frame: Month 12, Month 18, Month 24

  3. Progression Free Survival (PFS)

    PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    Time frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

  4. Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24

    PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    Time frame: Week 12, Week 24

  5. Time to Progression (TTP)

    TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.

    Time frame: from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])

  6. Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)

    Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations \>=4 weeks apart, no evidence of PD. PR: \>=50% ↓ in sum of products of longest diameter \& greatest perpendicular diameter of all target lesions compared to baseline by 2 observations \>=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ \>=25% in sum of products of longest diameter \& greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of \>= 1 new lesion.

    Time frame: BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.

  7. Determination of Best Overall Response Rate (BORR)

    Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.

    Time frame: Up to week 24

  8. Time to Response

    Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.

    Time frame: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

  9. Duration of Response

    Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).

    Time frame: from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])

  10. Disease Control Rate (DCR)

    Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.

    Time frame: Up to week 24

  11. Delayed Response (Response Beyond Week 24)

    Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.

    Time frame: from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])

  12. 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

    The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).

    Time frame: Baseline (Day 1, Cycle1), Week 12

  13. Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death

    An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.

    Time frame: On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

  14. Percentage of Participants With Immune-Related Adverse Events (irAEs)

    An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.

    Time frame: On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

  15. Percentage of Participants With Worst On-Study Hematological Abnormalities

    ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    Time frame: On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

  16. Percentage of Participants With Worst On-Study Liver Abnormalities

    ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    Time frame: On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

  17. Percentage of Participants With Worst On-Study Renal Abnormalities

    CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    Time frame: On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

  18. Clinically Meaningful Changes in Vital Signs and Physical Examinations

    Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.

    Time frame: vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter

07

Results

Posted Jun 23, 2011

Participant flow

Participant flow — Overall Study
MilestoneIpilimumab Plus gp100Ipilimumab Monotherapygp100
Started403137136
Treated381131131
Completed823110
Not completed321106126
Withdrew: Death306100119
Withdrew: Subject withdrew consent1023
Withdrew: Other222
Withdrew: Lost to follow-up321
Withdrew: Protocol violation001

Outcome measures

PrimaryOverall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone

OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

Time frame:
From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Reported as:
Median · months
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
monthsIpilimumab Plus gp100gp100
Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone9.95 (8.48 to 11.50)6.44 (5.49 to 8.71)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · Stratified Log Rank · p = 0.0004 · Hazard ratio (hr): 0.68 · 95% CI 0.55 to 0.85Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
SecondaryOverall 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

OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

Time frame:
From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Reported as:
Median · months
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
monthsIpilimumab Plus gp100Ipilimumab Monotherapygp100
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 Monotherapy9.95 (8.48 to 11.50)10.12 (8.02 to 13.80)6.44 (5.49 to 8.71)
Statistical analysis
  • Ipilimumab Monotherapy vs gp100 · Stratified Log Rank · p = 0.0026 · Hazard ratio (hr): 0.66 · 95% CI 0.51 to 0.87Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · Stratified Log Rank · p = 0.7575 · Hazard ratio (hr): 1.04 · 95% CI 0.83 to 1.30Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
Secondary12-, 18-, and 24-Month Survival Rates

The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.

Time frame:
Month 12, Month 18, Month 24
Reported as:
Number · probability
12-, 18-, and 24-Month Survival Rates
probabilityIpilimumab Plus gp100Ipilimumab Monotherapygp100
12-Month Survival Rate0.436 (0.386 to 0.485)0.456 (0.370 to 0.541)0.253 (0.181 to 0.329)
18-Month Survival Rate0.300 (0.254 to 0.347)0.332 (0.249 to 0.417)0.163 (0.101 to 0.230)
24-Month Survival Rate0.216 (0.172 to 0.261)0.235 (0.160 to 0.315)0.137 (0.080 to 0.200)
SecondaryProgression Free Survival (PFS)

PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

Time frame:
From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Reported as:
Median · months
Progression Free Survival (PFS)
monthsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Progression Free Survival (PFS)2.76 (2.73 to 2.79)2.86 (2.76 to 3.02)2.76 (2.73 to 2.83)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · Hazard ratio (hr): 0.81 · 95% CI 0.66 to 1.00Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
  • Ipilimumab Monotherapy vs gp100 · Hazard ratio (hr): 0.64 · 95% CI 0.50 to 0.83Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · Hazard ratio (hr): 1.25 · 95% CI 1.01 to 1.53Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
SecondaryPercentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24

PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

Time frame:
Week 12, Week 24
Reported as:
Median · percentage of participants
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Week 120.491 (0.441 to 0.539)0.577 (0.489 to 0.655)0.485 (0.396 to 0.567)
Week 240.164 (0.129 to 0.203)0.240 (0.171 to 0.315)0.100 (0.056 to 0.159)
SecondaryTime to Progression (TTP)

TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.

Time frame:
from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])
Reported as:
Median · months
Time to Progression (TTP)
monthsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Time to Progression (TTP)2.76 (2.73 to 2.79)2.86 (2.76 to 3.02)2.76 (2.73 to 2.83)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · Hazard ratio (hr): 0.81 · 95% CI 0.66 to 1.00Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
  • Ipilimumab Monotherapy vs gp100 · Hazard ratio (hr): 0.64 · 95% CI 0.50 to 0.83Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · Hazard ratio (hr): 1.25 · 95% CI 1.01 to 1.53Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
SecondaryBest Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)

Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations \>=4 weeks apart, no evidence of PD. PR: \>=50% ↓ in sum of products of longest diameter \& greatest perpendicular diameter of all target lesions compared to baseline by 2 observations \>=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ \>=25% in sum of products of longest diameter \& greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of \>= 1 new lesion.

Time frame:
BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.
Reported as:
Number · participants
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Complete Response120
Partial Response22132
Stable Disease582413
Progressed Disease2397089
Not Evaluated, Missing, or Unknown832832
SecondaryDetermination of Best Overall Response Rate (BORR)

Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.

Time frame:
Up to week 24
Reported as:
Number · percentage of participants
Determination of Best Overall Response Rate (BORR)
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Determination of Best Overall Response Rate (BORR)5.7 (3.7 to 8.4)10.9 (6.3 to 17.4)1.5 (0.2 to 5.2)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · Cochran-Mantel-Haenszel · p = 0.0433 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
  • Ipilimumab Monotherapy vs gp100 · Cochran-Mantel-Haenszel · p = 0.0012 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · Cochran-Mantel-Haenszel · p = 0.0402 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
SecondaryTime to Response

Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.

Time frame:
From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
Reported as:
Mean · months
Time to Response
monthsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Time to Response3.324 ± 0.95613.176 ± 0.76292.743 ± 0.0697
SecondaryDuration of Response

Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).

Time frame:
from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
Reported as:
Median · months
Duration of Response
monthsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Duration of Response11.47 (5.36 to NA)NA (28.09 to NA)NA (2.00 to NA)
SecondaryDisease Control Rate (DCR)

Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.

Time frame:
Up to week 24
Reported as:
Number · percentage of participants
Disease Control Rate (DCR)
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Disease Control Rate (DCR)20.1 (16.3 to 24.3)28.5 (21.1 to 36.8)11.0 (6.3 to 17.5)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · Cochran-Mantel-Haenszel · p = 0.0179 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
  • Ipilimumab Monotherapy vs gp100 · Cochran-Mantel-Haenszel · p = 0.0002 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · Cochran-Mantel-Haenszel · p = 0.0429 (P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).)
SecondaryDelayed Response (Response Beyond Week 24)

Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.

Time frame:
from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
Reported as:
Number · participants
Delayed Response (Response Beyond Week 24)
participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Complete Response Beyond Week 24130
Partial Response Beyond Week 24320
Stable Disease Beyond Week 24300
SecondaryChange 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

The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).

Time frame:
Baseline (Day 1, Cycle1), Week 12
Reported as:
Least squares mean · units on a scale
Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12
units on a scaleIpilimumab Plus gp100Ipilimumab Monotherapygp100
Global QOL (n=226, 83, 77)-7.4 (-10.4 to -4.3)-8.8 (-13.5 to -4.1)-10.4 (-15.3 to -5.5)
Physical (n=226 83, 78)-6.2 (-8.9 to -3.4)-5.1 (-9.4 to -0.8)-10.1 (-14.5 to -5.7)
Role Change (n=226, 83, 78)-9.3 (-13.4 to -5.3)-10.5 (-16.8 to -4.1)-13.7 (-20.2 to -7.2)
Cognitive (n=226, 83, 78)-3.1 (-5.8 to -0.3)-4.3 (-8.6 to 0.0)-3.4 (-7.8 to 1.0)
Emotional (n=227, 83, 78)-1.5 (-4.2 to 1.1)-3.6 (-7.7 to 0.6)-1.5 (-5.8 to 2.7)
Social (n=227, 83, 76)-5.6 (-9.2 to -2.0)-7.5 (-13.2 to -1.9)-4.2 (-10.1 to 1.8)
Fatigue (n=226, 82, 78)10.6 (7.0 to 14.1)12.5 (7.0 to 18.1)14.5 (8.8 to 20.2)
Nausea and Vomiting (n=226, 83, 78)4.6 (1.9 to 7.3)3.1 (-1.0 to 7.3)4.4 (0.1 to 8.7)
Pain (n=227, 83, 78)5.6 (2.0 to 9.3)7.9 (2.2 to 13.6)11.9 (6.0 to 17.7)
Dyspnea (n=222, 81, 77)3.5 (0.0 to 6.9)5.3 (-0.1 to 10.7)9.1 (3.6 to 14.6)
Sleep Disturbance (n=225, 83, 76)6.5 (2.3 to 10.7)10.1 (3.6 to 16.6)11.0 (4.3 to 17.8)
Appetite Loss (n=225, 83, 78)8.5 (4.4 to 12.5)11.6 (5.3 to 17.9)10.3 (3.8 to 16.8)
Constipation (n=225, 83, 77)5.2 (1.7 to 8.7)1.9 (-3.5 to 7.2)11.8 (6.2 to 17.4)
Diarrhea (n=223, 82, 78)6.4 (2.8 to 10.1)9.1 (3.4 to 14.7)2.1 (-3.7 to 7.9)
Financial Impact (n=226, 83, 76)0.0 (-3.2 to 3.2)3.1 (-1.9 to 8.1)1.7 (-3.5 to 6.9)
Statistical analysis
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.2805 · Mean difference (final values): 3.0 · 95% CI -2.5 to 8.6Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.6300 · Mean difference (final values): 1.6 · 95% CI -5.0 to 8.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.6026 · Mean difference (final values): 1.4 · 95% CI -3.9 to 6.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.1219 · Mean difference (final values): 3.9 · 95% CI -1.1 to 8.9Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.0978 · Mean difference (final values): 5.0 · 95% CI -0.9 to 11.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.6590 · Mean difference (final values): -1.1 · 95% CI -6.0 to 3.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.2480 · Mean difference (final values): 4.3 · 95% CI -3.0 to 11.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.4742 · Mean difference (final values): 3.2 · 95% CI -5.6 to 12.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.7597 · Mean difference (final values): 1.1 · 95% CI -6.1 to 8.3Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.9119 · Mean difference (final values): 0.3 · 95% CI -4.7 to 5.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.7616 · Mean difference (final values): -0.9 · 95% CI -6.9 to 5.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.6266 · Mean difference (final values): 1.2 · 95% CI -3.6 to 6.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.9984 · Mean difference (final values): 0.0 · 95% CI -4.8 to 4.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.4873 · Mean difference (final values): -2.0 · 95% CI -7.8 to 3.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.3938 · Mean difference (final values): 2.0 · 95% CI -2.7 to 6.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.6695 · Mean difference (final values): -1.4 · 95% CI -8.1 to 5.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.4041 · Mean difference (final values): -3.4 · 95% CI -11.3 to 4.6Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.5538 · Mean difference (final values): 1.9 · 95% CI -4.5 to 8.3Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.2259 · Mean difference (final values): -3.9 · 95% CI -10.3 to 2.4Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.6168 · Mean difference (final values): -2.0 · 95% CI -9.6 to 5.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.5329 · Mean difference (final values): -2.0 · 95% CI -8.2 to 4.3Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.9397 · Mean difference (final values): 0.2 · 95% CI -4.7 to 5.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.6716 · Mean difference (final values): -1.3 · 95% CI -7.1 to 4.6Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.5497 · Mean difference (final values): 1.4 · 95% CI -3.3 to 6.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.0625 · Mean difference (final values): -6.3 · 95% CI -12.8 to 0.3Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.3214 · Mean difference (final values): -4.0 · 95% CI -11.9 to 3.9Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.4898 · Mean difference (final values): -2.3 · 95% CI -8.7 to 4.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.0761 · Mean difference (final values): -5.6 · 95% CI -11.8 to 0.6Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.3187 · Mean difference (final values): -3.8 · 95% CI -11.2 to 3.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.5548 · Mean difference (final values): -1.8 · 95% CI -7.9 to 4.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.2450 · Mean difference (final values): -4.5 · 95% CI -12.1 to 3.1Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.8464 · Mean difference (final values): -0.9 · 95% CI -10.0 to 8.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.3351 · Mean difference (final values): -3.6 · 95% CI -10.9 to 3.7Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.6291 · Mean difference (final values): -1.8 · 95% CI -9.1 to 5.5Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.7675 · Mean difference (final values): 1.3 · 95% CI -7.4 to 10.1Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.3911 · Mean difference (final values): -3.1 · 95% CI -10.2 to 4.0Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.0431 · Mean difference (final values): -6.5 · 95% CI -12.9 to -0.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.0101 · Mean difference (final values): -9.9 · 95% CI -17.4 to -2.4Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.2796 · Mean difference (final values): 3.4 · 95% CI -2.8 to 9.5Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.1940 · Mean difference (final values): 4.3 · 95% CI -2.2 to 10.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.0821 · Mean difference (final values): 6.9 · 95% CI -0.9 to 14.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.4169 · Mean difference (final values): -2.6 · 95% CI -9.0 to 3.8Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs gp100 · ANCOVA · p = 0.5717 · Mean difference (final values): -1.7 · 95% CI -7.5 to 4.2Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Monotherapy vs gp100 · ANCOVA · p = 0.6949 · Mean difference (final values): 1.4 · 95% CI -5.6 to 8.4Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
  • Ipilimumab Plus gp100 vs Ipilimumab Monotherapy · ANCOVA · p = 0.2849 · Mean difference (final values): -3.1 · 95% CI -8.8 to 2.6Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
SecondaryPercentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death

An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.

Time frame:
On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Reported as:
Number · percentage of participants
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Any On-Study AE98.496.997.0
Severe (>=Grade 3) On-Study AEs50.855.052.3
Serious On-Study AEs40.842.039.4
Related On-Study AEs88.980.278.8
On-Study AEs Leading to Discontinuation9.213.03.8
AEs with Outcome of Death6.19.96.1
Related AE with Outcome of Death2.13.11.5
SecondaryPercentage of Participants With Immune-Related Adverse Events (irAEs)

An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.

Time frame:
On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Reported as:
Number · percentage of participants
Percentage of Participants With Immune-Related Adverse Events (irAEs)
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Any On-Study irAEs58.261.131.8
On-Study Severe irAEs11.315.33.0
On-Study Serious irAEs10.513.00.8
On-Study irAEs Leading to Discontinuation5.88.40.8
Death Due to irAEs1.31.50
Gastrointestinal irAEs (any grade)32.129.014.4
Severe (>= Grade 3) Gastrointestinal irAEs6.37.60.8
Liver irAEs (any grade)2.13.84.5
Severe (>= Grade 3) Liver irAEs1.10.82.3
Endocrine irAEs (any grade)3.97.61.5
Severe (>= Grade 3) Endocrine irAEs1.13.80
Skin irAEs (any grade)40.043.516.7
Severe (>= Grade 3) Skin irAEs2.41.50
Neurological irAEs (any grade)0.500
Severe (>= Grade 3) Neurological irAEs0.500
Other irAEs (any grade)3.24.62.3
Severe (>= Grade 3) Other irAEs1.62.30.8
SecondaryPercentage of Participants With Worst On-Study Hematological Abnormalities

ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

Time frame:
On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Reported as:
Number · percentage of participants
Percentage of Participants With Worst On-Study Hematological Abnormalities
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Hemoglobin, Grade 0 (n=352, 121, 126)48.944.646.8
Hemoglobin, Grade 1 (n=352, 121, 126)37.240.534.1
Hemoglobin, Grade 2 (n=352, 121, 126)12.214.015.1
Hemoglobin, Grade 3 (n=352, 121, 126)1.70.84.0
Hemoglobin, Grade 4 (n=352, 121, 126)000
Hemoglobin, Grade 1-4 (n=352, 121, 126)51.155.453.2
Hemoglobin, Grade 3-4 (n=352, 121, 126)1.70.84.0
White Blood Cells, Grade 0 (n=352, 121, 126)97.295.992.9
White Blood Cells, Grade 1 (n=352, 121, 126)1.41.75.6
White Blood Cells, Grade 2 (n=352, 121, 126)1.12.51.6
White Blood Cells, Grade 3 (n=352, 121, 126)0.300
White Blood Cells, Grade 4 (n=352, 121, 126)000
White Blood Cells, Grade 1-4 (n=352, 121, 126)2.84.17.1
White Blood Cells, Grade 3-4 (n=352, 121, 126)0.300
ANC, Grade 0 (n=352, 121, 126)95.593.496.0
ANC, Grade 1 (n=352, 121, 126)2.83.32.4
ANC, Grade 2 (n=352, 121, 126)0.92.50.8
ANC, Grade 3 (n=352, 121, 126)0.60.80.8
ANC, Grade 4 (n=352, 121, 126)0.300
ANC, Grade 1-4 (n=352, 121, 126)4.56.64.0
ANC, Grade 3-4 (n=352, 121, 126)0.90.80.8
Platelet Count, Grade 0 (n=349, 121, 126)94.690.191.3
Platelet Count, Grade 1 (n=349, 121, 126)4.99.18.7
Platelet Count, Grade 2 (n=349, 121, 126)0.60.80
Platelet Count, Grade 3 (n=349, 121, 126)000
Platelet Count, Grade 4 (n=349, 121, 126)000
Platelet Count, Grade 1-4 (n=349, 121, 126)5.49.98.7
Platelet Count, Grade 3-4 (n=349, 121, 126)000
Lymphocytes (absolute), Grade 0 (n=352, 121, 126)33.834.722.2
Lymphocytes (absolute), Grade 1 (n=352, 121, 126)46.347.942.9
Lymphocytes (absolute), Grade 2 (n=352, 121, 126)15.114.925.4
Lymphocytes (absolute), Grade 3 (n=352, 121, 126)4.32.59.5
Lymphocytes (absolute), Grade 4 (n=352, 121, 126)0.600
Lymphocytes (absolute), Grade 1-4(n=352, 121, 126)66.265.377.8
Lymphocytes (absolute), Grade 3-4(n=352, 121, 126)4.82.59.5
SecondaryPercentage of Participants With Worst On-Study Liver Abnormalities

ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

Time frame:
On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Reported as:
Number · percentage of participants
Percentage of Participants With Worst On-Study Liver Abnormalities
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
ALT, Grade 0 (n=352, 121, 126)83.276.084.9
ALT, Grade 1 (n=352, 121, 126)13.619.012.7
ALT, Grade 2 (n=352, 121, 126)2.03.31.6
ALT, Grade 3 (n=352, 121, 126)0.91.70.8
ALT, Grade 4 (n=352, 121, 126)0.300
ALT, Grade 1-4 (n=352, 121, 126)16.824.015.1
ALT, Grade 3-4 (n=352, 121, 126)1.11.70.8
AST, Grade 0 (n=352, 121, 126)80.471.981.7
AST, Grade 1 (n=352, 121, 126)16.523.115.1
AST, Grade 2 (n=352, 121, 126)1.43.32.4
AST, Grade 3 (n=352, 121, 126)1.41.70.8
AST, Grade 4 (n=352, 121, 126)0.300
AST, Grade 1-4 (n=352, 121, 126)19.628.118.3
AST, Grade 3-4 (n=352, 121, 126)1.71.70.8
Total Bilirubin, Grade 0 (n=353, 121, 127)95.593.498.4
Total Bilirubin, Grade 1 (n=353, 121, 127)2.54.10.8
Total Bilirubin, Grade 2 (n=353, 121, 127)1.41.70.8
Total Bilirubin, Grade 3 (n=353, 121, 127)0.60.80
Total Bilirubin, Grade 4 (n=353, 121, 127)000
Total Bilirubin, Grade 1-4 (n=353, 121, 127)4.56.61.6
Total Bilirubin, Grade 3-4 (n=353, 121, 127)0.60.80
Alkaline Phosphatase, Grade 0 (n=353, 121, 128)73.771.971.1
Alkaline Phosphatase, Grade 1 (n=353, 121, 128)19.820.724.2
Alkaline Phosphatase, Grade 2 (n=353, 121, 128)4.84.13.9
Alkaline Phosphatase, Grade 3 (n=353, 121, 128)1.73.30.8
Alkaline Phosphatase, Grade 4 (n=353, 121, 128)000
Alkaline Phosphatase, Grade 1-4 (n=353, 121, 128)26.328.128.9
Alkaline Phosphatase, Grade 3-4 (n=353, 121, 128)1.73.30.8
SecondaryPercentage of Participants With Worst On-Study Renal Abnormalities

CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

Time frame:
On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).
Reported as:
Number · percentage of participants
Percentage of Participants With Worst On-Study Renal Abnormalities
percentage of participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Creatinine, Grade 0 (n=353, 121, 128)89.588.488.3
Creatinine, Grade 1 (n=353, 121, 128)8.89.99.4
Creatinine, Grade 2 (n=353, 121, 128)1.41.72.3
Creatinine, Grade 3 (n=353, 121, 128)0.300
Creatinine, Grade 4 (n=353, 121, 128)000
Creatinine, Grade 1-4 (n=353, 121, 128)10.511.611.7
Creatinine, Grade 3-4 (n=353, 121, 128)0.300
SecondaryClinically Meaningful Changes in Vital Signs and Physical Examinations

Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.

Time frame:
vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter
Reported as:
Number · participants
Clinically Meaningful Changes in Vital Signs and Physical Examinations
participantsIpilimumab Plus gp100Ipilimumab Monotherapygp100
Clinically Meaningful Vital Sign Changes000
Clinically Meaningful Physical Examination Changes000

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ipilimumab Monotherapy—55/131 (42%)124/131 (94.7%)
Ipilimumab Plus gp100—155/380 (40.8%)362/380 (95.3%)
gp100—52/132 (39.4%)124/132 (93.9%)
Most frequent serious events
Showing 10 of 209
Most frequent serious events
EventIpilimumab MonotherapyIpilimumab Plus gp100gp100
COLITISGastrointestinal disorders7/13114/3800/132
DYSPNOEARespiratory, thoracic and mediastinal disorders3/1312/3807/132
DIARRHOEAGastrointestinal disorders6/13116/3800/132
ABDOMINAL PAINGastrointestinal disorders2/1314/3805/132
ANAEMIABlood and lymphatic system disorders4/1315/3805/132
DEHYDRATIONMetabolism and nutrition disorders1/1318/3804/132
NAUSEAGastrointestinal disorders2/1316/3804/132
PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders2/1315/3804/132
ASTHENIAGeneral disorders3/1314/3801/132
HYPOTENSIONVascular disorders3/1311/3802/132
Most frequent other events
Showing 10 of 43
Most frequent other events
EventIpilimumab MonotherapyIpilimumab Plus gp100gp100
FATIGUEGeneral disorders55/131137/38041/132
DIARRHOEAGastrointestinal disorders41/131142/38026/132
NAUSEAGastrointestinal disorders44/131127/38049/132
PRURITUSSkin and subcutaneous tissue disorders39/13179/38014/132
INJECTION SITE REACTIONGeneral disorders2/131109/38026/132
CONSTIPATIONGastrointestinal disorders27/13179/38034/132
DECREASED APPETITEMetabolism and nutrition disorders33/13185/38029/132
VOMITINGGastrointestinal disorders30/13171/38027/132
RASHSkin and subcutaneous tissue disorders29/13178/3809/132
PYREXIAGeneral disorders15/13174/38023/132

Baseline characteristics

Age Continuous
Age Continuous(years)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
Mean55.6 (24 to 84)56.8 (19 to 88)57.4 (23 to 90)56.2 (19 to 90)
Age, Customized
Age, Customized(participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
< 65 years2919594480
>=65 years1124242196
Sex: Female, Male
Sex: Female, Male(Participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
Female1565663275
Male2478173401
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
White380129129638
Black3115
Hispanic187530
Other2013
Duration of Melanoma
Duration of Melanoma(years)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
Mean5.09 (0.2 to 38.9)4.34 (-0.0 to 35.9)5.65 (0.3 to 31.2)5.05 (-0.0 to 38.9)
Melanoma Stage
Melanoma Stage(Participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
M051410
M1a37141162
M1b762223121
M1c28510098483
Prior Interleukin-2 Therapy
Prior Interleukin-2 Therapy(Participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
No314105103522
Yes893233154
Lactate Dehydrogenase
Lactate Dehydrogenase(Participants)Ipilimumab Plus gp100Ipilimumab Monotherapygp100Total
>upper limit of normal (ULN)1495352254
<=ULN2528481417
unknown2035
08

Study locations

209 sites
  • Arizona Cancer Center
    Tucson, Arizona 85724, United States
  • University Medical Center
    Tucson, Arizona 85724, United States
  • City of Hope National Medical Center
    Duarte, California 91010, United States
  • San Diego Cancer Center
    Encinitas, California 92024, United States
  • La Jolla Hematology and Oncology Medical Group
    La Jolla, California 92037, United States
  • Scripps Cancer Center
    La Jolla, California 92037, United States
  • Moores UCSD Cancer Center
    La Jolla, California 92093, United States
  • Pacific Shores Medical Group
    Long Beach, California 90813, United States
  • Cancer Institute Medical Group, Inc
    Los Angeles, California 90025, United States
  • The Angeles Clinic and Research Institute
    Los Angeles, California 90025, United States
  • USC/Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • North County Oncology Medical Clinical, Inc.
    Oceanside, California 92056, United States
  • City of Hope Medical Group
    Pasadena, California 91105, United States
  • University of California, San Diego
    San Diego, California 92103, United States
  • St. Mary's Medical Center - Northern California Melanoma Center
    San Francisco, California 94109, United States
  • Cancer Institute Medical Group, Inc
    Santa Monica, California 90404, United States
  • San Diego Cancer Center
    Vista, California 92081, United States
  • Anschutz Cancer Pavilion
    Aurora, Colorado 80010, United States
  • Rocky Mountain Cancer Centers
    Aurora, Colorado 80012, United States
  • University of Colorado Health Sciences Center
    Aurora, Colorado 80045, United States
  • Rocky Mountain Cancer Centers
    Boulder, Colorado 80304, United States
  • Rocky Mountain Cancer Centers
    Colorado Springs, Colorado 80909, United States
  • Rocky Mountain Cancer Centers
    Denver, Colorado 80218, United States
  • University of Colorado Hospital
    Denver, Colorado 80262, United States
  • Rocky Mountain Cancer Centers
    Lakewood, Colorado 80228, United States
  • Rocky Mountain Cancer Centers
    Littleton, Colorado 80120, United States
  • Rocky Mountain Cancer Centers
    Lone Tree, Colorado 80124, United States
  • Rocky Mountain Cancer Centers
    Longmont, Colorado 80501, United States
  • Yale University School of Medicine - Oncology Outpatient Clinic
    New Haven, Connecticut 06520, United States
  • Mount Sinai Comprehensive Cancer Center at Aventura
    Aventura, Florida 33180, United States
  • Memorial Regional Cancer Center
    Hollywood, Florida 33021, United States
  • Shands Jacksonville
    Jacksonville, Florida 32209, United States
  • University of Florida/Jacksonville Faculty Clinic
    Jacksonville, Florida 32209, United States
  • Mount Sinai Comprehensive Cancer Center
    Miami Beach, Florida 33140, United States
  • Mount Sinai Medical Center
    Miami Beach, Florida 33140, United States
  • Jackson Memorial Hospital & Clinics
    Miami, Florida 33136, United States
  • University of Miami Hospital & Clinics
    Miami, Florida 33136, United States
  • M.D. Anderson Cancer Center Orlando
    Orlando, Florida 32806, United States
  • Palm Beach Cancer Institute
    Palm Beach Gardens, Florida 33410, United States
  • H. Lee Moffitt Cancer Center & Research Institute
    Tampa, Florida 33612, United States
  • Palm Beach Cancer Institute
    Wellington, Florida 33414, United States
  • Palm Beach Cancer Institute
    West Palm Beach, Florida 33401, United States
  • Emory University Hospital-Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Cancer Care Specialists of Central IL
    Decatur, Illinois 62526, United States
  • Decatur Memorial Hospital
    Decatur, Illinois 62526, United States
  • Cancer Care Specialists of Central IL
    Effingham, Illinois 62401, United States
  • Cardinal Bernardin Cancer Center, Loyola Unv. Med. Ctr.
    Maywood, Illinois 60153, United States
  • Center for Cancer Care at Goshen Health System
    Goshen, Indiana 46526, United States
  • Indiana Oncology Hematology Consultants North
    Indianapolis, Indiana 46202, United States
  • American Health Network of IN, LLC
    Indianapolis, Indiana 46237, United States
  • Indiana Oncology Hematology South
    Indianapolis, Indiana 46237, United States
  • Indiana Oncology Hematology Consutants of Noblesville
    Noblesville, Indiana 46060, United States
  • Central Baptist Hospital
    Lexington, Kentucky 40503, United States
  • James Graham Brown Cancer Center
    Louisville, Kentucky 40202, United States
  • Norton Hospital
    Louisville, Kentucky 40202, United States
  • University of Louisville Hospital
    Louisville, Kentucky 40202, United States
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Baltimore, Maryland 21231, United States
  • Franklin Square Hospital Center
    Baltimore, Maryland 21237, United States
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Lutherville, Maryland 21093, United States
  • Beth Isreal Dec Medical Center
    Boston, Massachusetts 02115, United States
  • Brigham and Womens Hospital
    Boston, Massachusetts 02115, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Henry Ford Medical Center
    Dearborn, Michigan 48126, United States
  • Henry Ford Hospital
    Detroit, Michigan 48202, United States
  • Henry Ford Medical Center- West Bloomfield
    West Bloomfield, Michigan 48322, United States
  • Humphrey Cancer Center
    Coon Rapids, Minnesota 55433, United States
  • Humphrey Cancer Center
    Fridley, Minnesota 55432, United States
  • Hubert H Humphrey Cancer Center
    Robbinsdale, Minnesota 55422, United States
  • Family Cancer Center
    Olive Branch, Mississippi 38654, United States
  • Ellis Fischel Cancer Center
    Columbia, Missouri 65203, United States
  • St. Joseph Oncology, Inc
    St. Joseph, Missouri 64507, United States
  • Barnes Jewish Hospital
    St. Louis, Missouri 63110, United States
  • Washington Unv. School of Med./ Siteman Cancer Center
    St. Louis, Missouri 63110, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • The Cancer Center at Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Hematology-Oncology Associates of Northern NJ, PA
    Morristown, New Jersey 07962, United States
  • Robert Wood Johnson University Hospital
    New Brunswick, New Jersey 08901, United States
  • The Cancer Institute of New Jersey
    New Brunswick, New Jersey 08901, United States
  • Overlook Oncology Center
    Summit, New Jersey 07901, United States
  • New Mexico Oncology Hematology Consultants, Ltd.
    Albuquerque, New Mexico 87109, United States
  • Hematology-Oncology Associates of CNY
    East Syracuse, New York 13057, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10021, United States
  • Columbia University Medical Center, Irving Center for Clinical Research
    New York, New York 10032, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599-7050, United States
  • The Christ Hospital Cancer Center
    Cincinnati, Ohio 45219, United States
  • The Cleveland Clinic Foundation
    Cleveland, Ohio 44195, United States
  • Providence Portland Medical Center
    Portland, Oregon 97213, United States
  • The Oregon Clinical
    Portland, Oregon 97213, United States
  • Penn State Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
  • Thomas Jefferson University Hosptital
    Philadelphia, Pennsylvania 19107, United States
  • Fox Chase Cancer Center
    Philadelphia, Pennsylvania 19111, United States
  • Hillman Cancer Research Pavilion
    Pittsburgh, Pennsylvania 15213, United States
  • Hillman Cancer Center
    Pittsburgh, Pennsylvania 15232, United States
  • University of Pittsburgh Cancer Institute
    Pittsburgh, Pennsylvania 15232, United States
  • Cancer Centers of the Carolinas
    Easley, South Carolina 29640, United States
  • Cancer Centers of the Carolinas
    Greenville, South Carolina 29615, United States
  • Cancer Centers of the Carolinas
    Seneca, South Carolina 29672, United States
  • Cancer Centers of the Carolinas
    Spartanburg, South Carolina 29307, United States
  • Family Cancer Center
    Bartlett, Tennessee 38133, United States
  • Family Cancer Center
    Collierville, Tennessee 38017, United States

Showing the first 100 of 209 sites across 13 countries.

09

References and documents

Publications

  • Larkin J, Hatswell AJ, Nathan P, Lebmeier M, Lee D. The Predicted Impact of Ipilimumab Usage on Survival in Previously Treated Advanced or Metastatic Melanoma in the UK. PLoS One. 2015 Dec 23;10(12):e0145524. doi: 10.1371/journal.pone.0145524. eCollection 2015. PubMed 26700304 ↗
  • Koguchi Y, Hoen HM, Bambina SA, Rynning MD, Fuerstenberg RK, Curti BD, Urba WJ, Milburn C, Bahjat FR, Korman AJ, Bahjat KS. Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab. Cancer Res. 2015 Dec 1;75(23):5084-92. doi: 10.1158/0008-5472.CAN-15-2303. PubMed 26627641 ↗
  • Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9. PubMed 25667295 ↗
  • Johnson DB, Friedman DL, Berry E, Decker I, Ye F, Zhao S, Morgans AK, Puzanov I, Sosman JA, Lovly CM. Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center. Cancer Immunol Res. 2015 May;3(5):464-9. doi: 10.1158/2326-6066.CIR-14-0217. Epub 2015 Feb 3. PubMed 25649350 ↗
  • Hatswell AJ, Pennington B, Pericleous L, Rowen D, Lebmeier M, Lee D. Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death. Health Qual Life Outcomes. 2014 Sep 10;12:140. doi: 10.1186/s12955-014-0140-1. PubMed 25214238 ↗
  • McDermott D, Haanen J, Chen TT, Lorigan P, O'Day S; MDX010-20 investigators. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol. 2013 Oct;24(10):2694-2698. doi: 10.1093/annonc/mdt291. Epub 2013 Aug 13. PubMed 23942774 ↗
  • Robert C, Schadendorf D, Messina M, Hodi FS, O'Day S; MDX010-20 investigators. Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control. Clin Cancer Res. 2013 Apr 15;19(8):2232-9. doi: 10.1158/1078-0432.CCR-12-3080. Epub 2013 Feb 26. PubMed 23444228 ↗
  • Weber JS, Dummer R, de Pril V, Lebbe C, Hodi FS; MDX010-20 Investigators. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013 May 1;119(9):1675-82. doi: 10.1002/cncr.27969. Epub 2013 Feb 7. PubMed 23400564 ↗
  • Revicki DA, van den Eertwegh AJ, Lorigan P, Lebbe C, Linette G, Ottensmeier CH, Safikhani S, Messina M, Hoos A, Wagner S, Kotapati S. Health related quality of life outcomes for unresectable stage III or IV melanoma patients receiving ipilimumab treatment. Health Qual Life Outcomes. 2012 Jun 13;10:66. doi: 10.1186/1477-7525-10-66. PubMed 22694829 ↗
  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5. Erratum In: N Engl J Med. 2010 Sep 23;363(13):1290. PubMed 20525992 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 11, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00094653
Lead sponsor
Bristol-Myers Squibb
First posted
Oct 22, 2004
Start date
Sep 2004
Primary completion
Aug 2009
Completion
Oct 2009
Results posted
Jun 23, 2011
Last update
Jul 11, 2011

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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