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

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)

Population: 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.

Time frame: Month 12, Month 18, Month 24

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.

Time frame: 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.

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

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 measure at given time points.

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

Population: All subjects who received at least 1 dose or any partial dose of study medication.

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])

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 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

Population: 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.

Time frame: Up to week 24

Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

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])

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.

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)

Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

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]).

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.

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]).

Population: All subjects who received at least 1 dose or any partial dose of study medication.

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

Population: Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.

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]).

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.

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]).

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.

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]).

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.

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)

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.

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])

Population: 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.

Time frame: 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.