Trial Outcomes & Findings for Study of Immunotherapy to Treat Advanced Prostate Cancer (NCT NCT00861614)

Last Updated: 2016-09-30

Results Overview

OS is defined as the time in months from randomization date to date of death due to any cause in all randomized subjects. For participants alive at the time of the database cutoff date, OS was censored at the last date the participant was known to be alive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

988 participants

Primary outcome timeframe

Date of randomization to date of death

Results posted on

2016-09-30

Participant Flow

988 enrolled, 799 randomized (399 ipilimumab, 400 placebo); 149 no longer met study criteria, 17 withdrew, 6 adverse events, 4 died, 1 lost to follow-up,12 unspecified. 789 treated with radiotherapy (393 ipilimumab, 396 placebo); 2 no longer met study criteria, 3 withdrew consent, 1 died, 2 adverse events, 2 lost to follow-up.

Participant milestones

Participant milestones
Measure	Ipilimumab + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gray units (Gy) to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Study STARTED	393	396
Overall Study COMPLETED	22	28
Overall Study NOT COMPLETED	371	368

Reasons for withdrawal

Reasons for withdrawal
Measure	Ipilimumab + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gray units (Gy) to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Study Disease Progression	182	263
Overall Study Study Drug Toxicity	79	6
Overall Study Death	32	19
Overall Study Adverse Event	27	23
Overall Study Withdrawal by Subject	34	35
Overall Study Other	17	22

Baseline Characteristics

Study of Immunotherapy to Treat Advanced Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ipilimumab + Radiotherapy n=399 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4,7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=400 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed PD, drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Total n=799 Participants Total of all reporting groups
Age, Continuous	68.2 years STANDARD_DEVIATION 7.53 • n=5 Participants	67.1 years STANDARD_DEVIATION 7.56 • n=7 Participants	67.6 years STANDARD_DEVIATION 7.56 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	399 Participants n=5 Participants	400 Participants n=7 Participants	799 Participants n=5 Participants

PRIMARY outcome

Timeframe: Date of randomization to date of death

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=399 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=400 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Survival (OS)	11.04 months Interval 9.46 to 12.48	10.02 months Interval 8.38 to 11.17

PRIMARY outcome

Timeframe: Date of randomization to date of death

Population: All randomized participants

The overall survival (OS) rate is a percentage, representing the fraction of all randomized participants who were alive following treatment, from 1 to 5 years. OS was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=399 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=400 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Survival Rate OS Rate at Year 1	46.5 percentage of participants Interval 41.6 to 51.4	40.8 percentage of participants Interval 35.9 to 45.6
Overall Survival Rate OS Rate at Year 2	25.2 percentage of participants Interval 20.9 to 29.6	16.6 percentage of participants Interval 12.9 to 20.3
Overall Survival Rate OS Rate at Year 3	15.3 percentage of participants Interval 11.7 to 18.9	7.9 percentage of participants Interval 5.2 to 10.6
Overall Survival Rate OS Rate at Year 4	10.1 percentage of participants Interval 6.9 to 13.3	3.3 percentage of participants Interval 1.3 to 5.3
Overall Survival Rate OS Rate at Year 5	7.9 percentage of participants Interval 4.4 to 11.4	2.7 percentage of participants Interval 0.8 to 4.7

SECONDARY outcome

Timeframe: Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death

Population: All randomized participants

All PFS events were based on investigator's assessment. Participants who were alive and did not experience a PFS event were censored at the earlier of the latest prostate-specific antigen (PSA) or radiological tumor assessment date. Participants who did not die, showed no clinical deterioration, and who had no recorded post-baseline PSA or radiological tumor assessment were censored at randomization date.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=399 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=400 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Progression Free Survival (PFS)	4.01 months Interval 3.65 to 4.34	3.06 months Interval 2.86 to 3.42

SECONDARY outcome

Timeframe: Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit

Population: All pain-evaluable participants

The percentage of participants with a pain response assessed using the Brief Pain Inventory Short Form (BPI-SF) completed by participants throughout the study in a daily diary log. Pain-evaluable participants were defined as those with a decrease in the average daily worst pain intensity by at least 30% from baseline, maintained over 2 consecutive evaluations without the use of any rescue analgesic medication or increase in analgesic use in the same time period.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=197 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=186 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Pain Response	3.55 percentage of participants Interval 1.44 to 7.18	0.54 percentage of participants Interval 0.01 to 2.96

SECONDARY outcome

Timeframe: Day of initial pain response to day of completion of pain response or date of death

Population: All pain-evaluable participants with pain response

The time between the initial date of pain response and completion date of pain response. The initial date when the pain response criterion was achieved was considered the pain response date. The earlier of date of death, date of tumor resection surgery, or date when pain response criterion was no longer met was considered the completion date of the pain response. If none of these scenarios occurred, the completion of the pain response was set to the last known alive date.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=7 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=1 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Duration of Pain Response	2.5 months Interval 1.5 to 3.0	1.5 months CI not applicable due to only one participant

SECONDARY outcome

Timeframe: Randomization to date of death

Population: All treated participants

AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during study and up to 70 days after last dose. IrAEs=AEs potentially associated with inflammation and considered to be causally related to study drug and grouped into gastrointestinal (GI), hepatic, skin, endocrine and neurological. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies. IrAEs/ imARs were graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) SAE	257 participants	164 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Treatment-Related AE	296 participants	180 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Any Death	346 participants	371 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Deaths Due to Study Drug Toxicity	7 participants	1 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Discontinuation of Study Drug due to AEs	137 participants	62 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Immune-Related AE (any grade)	250 participants	86 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR) Immune-Mediated Adverse Reaction (Grade >=2)	203 participants	40 participants

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

The time between first dose of study drug and date of earliest Grade 3 or 4 irAE. These irAEs are AEs of unknown etiology, consistent with an immune phenomenon and considered as causally related to drug exposure. The five subcategories of irAE examined include gastrointestinal (GI), liver, skin, endocrine, and neurological and are graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Gastrotintestinal (n= 71,3)	5.71 weeks Interval 5.0 to 7.0	5.71 weeks Interval 0.57 to 31.86
Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Liver (n= 18,5)	9.14 weeks Interval 8.29 to 10.43	6.00 weeks Interval 3.14 to 8.57
Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Skin (n=4,0)	3.71 weeks Interval 2.57 to 6.43	NA weeks There were no participants in this treatment arm who displayed irAEs of this type
Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Endocrine (n=8,2)	7.93 weeks Interval 4.14 to 11.14	5.00 weeks Interval 4.29 to 5.71
Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Neurological (n= 1,0)	11.4 weeks CI not applicable due to only one participant	NA weeks There were no participants in this treatment arm who displayed irAEs of this type

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

Time between the date of onset of a Grade 3 or 4 irAE and the date of improvement to Grade 1 or less or the worst grade at baseline.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Liver (n=18,5)	4.1 weeks Interval 3.6 to 8.1	6.0 weeks Interval 1.9 to Number of subjects was too small to obtain upper limit
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Gastrointestinal (n=71,3)	2.9 weeks Interval 1.6 to 4.7	0.9 weeks Interval 0.4 to 1.1
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Skin (n=4,0)	3.6 weeks Interval 2.6 to 5.9	NA weeks There were no participants in this treatment arm who displayed irAEs of this type.
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Endocrine (n=8,2)	11.1 weeks Interval 2.4 to Number of subjects was too small to obtain upper limit	5.9 weeks Interval 0.9 to 10.9
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Neurological (n=1,0)	NA weeks No participant with resolved irAE.	NA weeks There were no participants in this treatment arm who displayed irAEs of this type.

SECONDARY outcome

Timeframe: Day 1 to time of onset of the imAR of interest

Population: All treated participants receiving Ipilimumab + Radiotherapy

The time between first dose of study drug and date of earliest Grade 3 or 4 imAR. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies and graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0. Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) Enterocolitis (n=65)	3.4 weeks Interval 0.3 to 16.6	—
Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) Hepatitis (n=17)	9.0 weeks Interval 1.7 to 16.9	—
Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) Dermatitis (n=3)	2.4 weeks Interval 0.1 to 3.1	—
Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) Endocrinopathies (n=6)	7.9 weeks Interval 1.7 to 10.7	—

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants receiving Ipilimumab + Radiotherapy

Time between the date of onset of an imAR to the date of resolution date of the event or the last known date participant was alive if an event did not resolve. Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 Enterocolitis (n=52)	6.0 weeks Interval 0.1 to 40.1	—
Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 Hepatitis (n=15)	8.6 weeks Interval 1.1 to 19.0	—
Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 Dermatitis (n=3)	6.9 weeks Interval 4.0 to 12.1	—
Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 Endocrinopathies (n=0)	NA weeks No participant with resolved imAR	—

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

Comparison of baseline versus worst grade hematology laboratory tests as measured by white blood count (WBC), absolute neutrophil count (ANC), platelet count, hemoglobin and lymphocyte results. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for WBC were based on Gr 1: 3.0 - \< Lower Limit of Normal (LLN); Gr 2: 2.0 - \< 3.0; Gr 3: 1.0 - \< 2.0; Gr4: \< 1.0. Abnormal values for Hemoglobin were based on Gr 1: 10.0 - \< LLN; Gr 2: 8.0 - \< 10.0; Gr 3: 6.5 - \< 8.0; Gr 4: \< 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - \< 1.5; Gr 2: 0.5 - \< 0.8; Gr 3): 0.2 - \< 0.5; Gr 4: \< 0.2. Abnormal values for ANC were based on Gr 1: 1.5 - \< 2.0; Gr 2: 1.0 - \< 1.5; Gr 3: 0.5 - \< 1.0; Gr 4: \< 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - \< LLN; Gr 2: 50.0 - \< 75.0; Gr 3: 25.0 - \< 50.0; Gr 4: \< 25.0.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Not Reported at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Gr 0 at Baseline to Gr 3-4	0 participants	3 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Gr 1 at Baseline to Gr 3-4	16 participants	25 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Gr 2 at Baseline to Gr 3-4	13 participants	11 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Gr 3 at Baseline to Gr 3-4	0 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Hemoglobin Not Reported at Baseline to Gr 3-4	0 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Gr 0 at Baseline to Gr 3-4	4 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Gr 1 at Baseline to Gr 3-4	6 participants	11 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Gr 2 at Baseline to Gr 3-4	11 participants	17 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Gr 3 at Baseline to Gr 3-4	8 participants	7 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lymphocytes Not Reported at Baseline to Gr 3-4	3 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Gr 0 at Baseline to Gr 3-4	3 participants	2 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Gr 1 at Baseline to Gr 3-4	0 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Gr 2 at Baseline to Gr 3-4	0 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Gr 3 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline WBC Not Reported at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Gr 0 at Baseline to Gr 3-4	4 participants	6 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Gr 1 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Gr 2 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Gr 3 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline ANC Not Reported at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Gr 0 at Baseline to Gr 3-4	1 participants	6 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Gr 1 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Gr 2 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Platelet Count Gr 3 at Baseline to Gr 3-4	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

Comparison of baseline versus worst grade liver function as measured by alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for ALP, ALT and AST were based on grades; Gr 1: \> 1.0 - 2.5 \* upper limits of normal (ULN); Gr 2: \> 2.5 - 5.0 \* ULN; Gr 3: \> 5.0 - 20.0 \* ULN; Gr 4: \> 20.0 \* ULN. Abnormal values for Total Bilirubin were based on Gr 1: \> 1.0 - 1.5 \* upper limits of normal (ULN); Gr 2: \> 1.5 - 3.0 \* ULN; Gr 3: \> 3.0 - 10.0 \* ULN; Gr 4: \> 10.0 \* ULN.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Gr 3 at Baseline to Gr 3-4	27 participants	42 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Gr 0 at Baseline to Gr 3-4	16 participants	1 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Gr 1 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Gr 2 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Gr 3 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALT Not reported at Basline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Gr 0 at Baseline to Gr 3-4	15 participants	6 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Gr 1 at Baseline to Gr 3-4	5 participants	1 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Gr 2 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Gr 3 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline AST Not Reported at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Gr 0 at Baseline to Gr 3-4	6 participants	2 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Gr 1 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Gr 2 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Gr 3 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Total Bilirubin Not Reported at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Gr 0 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Gr 1 at Baseline to Gr 3-4	10 participants	17 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Gr 2 at Baseline to Gr 3-4	21 participants	29 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Gr 4 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline ALP Not Reported at Baseline to Gr 3-4	0 participants	6 participants

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

Comparison of baseline versus worst grade serum chemistry as measured by lipase and amylase analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for lipase: Gr1: \> 1.0 - 1.5 \* ULN; Gr2: \> 1.5 - 2.0 \* ULN; Gr 3: \> 2.0 - 5.0 \* ULN; Gr4: \> 5.0\*ULN. Abnormal values for amylase: Gr1: \> 1.0 - 1.5 \* ULN; Gr 2: \> 1.5 - 2.0 \* ULN; Gr 3: \> 2.0 - 5.0 \* ULN; Gr4: \> 5.0 \* ULN.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Not reported at Basline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Gr 0 at Baseline to Gr 3-4	21 participants	10 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Gr 1 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Gr 2 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Lipase Gr 3 at Baseline to Gr 3-4	0 participants	1 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Gr 0 at Baseline to Gr 3-4	4 participants	4 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Gr 1 at Baseline to Gr 3-4	1 participants	1 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Gr 2 at Baseline to Gr 3-4	3 participants	1 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Gr 3 at Baseline to Gr 3-4	1 participants	0 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Gr 4 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Amylase Not Reported at Baseline to Gr 3-4	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to 70 days after last dose of study drug

Population: All treated participants

Comparison of baseline versus worst grade renal function as measured by creatinine analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).Gr 0: within normal range. Abnormal values for Creatinine were based on Gr 1: \> 1.0 - 1.5\*ULN; Gr 2: \> 1.5 - 3.0\*ULN; Gr 3: \> 3.0 - 6.0\*ULN; Gr 4: \> 6.0\*ULN.

Outcome measures

Outcome measures
Measure	Ipilimumab + Radiotherapy n=393 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 Participants Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Not Reported at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Gr 0 at Baseline to Gr 3-4	3 participants	3 participants
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Gr 1 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Gr 2 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Gr 3 at Baseline to Gr 3-4	0 participants	0 participants
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Creatinine Gr 4 at Baseline to Gr 3-4	0 participants	0 participants

Adverse Events

Ipilimumab + Radiotherapy

Serious events: 257 serious events

Other events: 350 other events

Deaths: 0 deaths

Placebo + Radiotherapy

Serious events: 164 serious events

Other events: 333 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Ipilimumab + Radiotherapy n=393 participants at risk Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.	Placebo + Radiotherapy n=396 participants at risk Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Nervous system disorders Headache	9.7% 38/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	7.8% 31/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Gastrointestinal disorders Abdominal pain	8.4% 33/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	6.3% 25/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Metabolism and nutrition disorders Decreased appetite	30.3% 119/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	24.5% 97/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Metabolism and nutrition disorders Dehydration	6.6% 26/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	3.8% 15/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Psychiatric disorders Depression	2.5% 10/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	5.1% 20/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Vascular disorders Hypertension	5.1% 20/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	3.3% 13/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Metabolism and nutrition disorders Hypokalaemia	5.1% 20/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	2.5% 10/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Psychiatric disorders Insomnia	7.9% 31/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	8.6% 34/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Skin and subcutaneous tissue disorders Pruritus	25.2% 99/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	5.6% 22/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Respiratory, thoracic and mediastinal disorders Cough	9.2% 36/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	6.8% 27/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Nervous system disorders Dizziness	5.6% 22/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	4.5% 18/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.0% 47/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	8.1% 32/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
General disorders Fatigue	36.6% 144/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	30.3% 120/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.1% 32/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	11.1% 44/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
General disorders Oedema peripheral	11.7% 46/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	8.3% 33/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
General disorders Pyrexia	20.6% 81/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	12.6% 50/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Investigations Aspartate aminotransferase increased	7.9% 31/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	5.3% 21/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Investigations Haemoglobin decreased	6.6% 26/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	5.1% 20/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Gastrointestinal disorders Nausea	32.1% 126/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	26.3% 104/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Skin and subcutaneous tissue disorders Rash	20.6% 81/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	6.8% 27/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Gastrointestinal disorders Diarrhoea	47.3% 186/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	23.7% 94/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Gastrointestinal disorders Constipation	16.8% 66/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	20.7% 82/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Musculoskeletal and connective tissue disorders Pain in extremity	7.9% 31/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	10.4% 41/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Infections and infestations Urinary tract infection	6.1% 24/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	6.1% 24/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Gastrointestinal disorders Vomiting	27.2% 107/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	20.2% 80/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Blood and lymphatic system disorders Anaemia	20.1% 79/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	20.5% 81/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
General disorders Asthenia	20.4% 80/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	16.2% 64/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
General disorders Pain	8.4% 33/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	11.1% 44/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Investigations Alanine aminotransferase increased	6.6% 26/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	2.3% 9/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Musculoskeletal and connective tissue disorders Arthralgia	11.2% 44/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	14.4% 57/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Musculoskeletal and connective tissue disorders Back pain	14.2% 56/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	18.7% 74/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Musculoskeletal and connective tissue disorders Bone pain	7.9% 31/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	13.4% 53/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015
Investigations Weight decreased	23.2% 91/393 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015	14.1% 56/396 • Day 1 to 70 days following the last dose of study drug Study initiated: May 2009; Study completed: August 2015