Trial Outcomes & Findings for Drug-Drug Interaction - 3 Arm - Carboplatin/Paclitaxel, Dacarbazine (NCT NCT00796991)

Last Updated: 2014-01-06

Results Overview

Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

Day 1 (0 h) to Day 43

Results posted on

2014-01-06

Participant Flow

17 February 2009 study initiated; last patient, last visit (LPLV) 30 October 2012.

72 enrolled; 59 randomized and treated with study drug. Reasons for non-randomization: 7 no longer met study criteria; 3 withdrew consent; 1 had target lesion \<1 cm; 1 had screening magnetic resonance imaging (MRI) showed brain metastases; 1 had adverse event.

Participant milestones

Participant milestones
Measure	Paclitaxel, Carboplatin, Ipilimumab Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Overall Study STARTED	20	19	20
Overall Study COMPLETED	5	7	6
Overall Study NOT COMPLETED	15	12	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Paclitaxel, Carboplatin, Ipilimumab Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Overall Study Adverse Event	0	0	1
Overall Study Death	2	0	0
Overall Study Disease Progression	10	9	7
Overall Study Study Drug Toxicity	3	3	5
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

Drug-Drug Interaction - 3 Arm - Carboplatin/Paclitaxel, Dacarbazine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Total n=59 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	20 Participants n=4 Participants
Age, Continuous	55 years STANDARD_DEVIATION 14 • n=5 Participants	54 years STANDARD_DEVIATION 17 • n=7 Participants	60 years STANDARD_DEVIATION 11 • n=5 Participants	57 years STANDARD_DEVIATION 14 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	38 Participants n=4 Participants
Region of Enrollment United States	20 participants n=5 Participants	19 participants n=7 Participants	20 participants n=5 Participants	59 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) 0	14 participants n=5 Participants	17 participants n=7 Participants	16 participants n=5 Participants	47 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) 1	6 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) 2	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Number of Target Lesions 1 lesion	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Number of Target Lesions 2 lesions	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Number of Target Lesions 3 lesions	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Number of Target Lesions 4 lesions	0 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants
Number of Target Lesions >=5 lesions	10 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (0 h) to Day 43

Population: N=participants who received study drug and with adequate Pharmacokinetic (PK) profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of Ipilimumab N=14, 14, 12	234.54 µg/mL Geometric Coefficient of Variation 29	246.50 µg/mL Geometric Coefficient of Variation 35	251.05 µg/mL Geometric Coefficient of Variation 34
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of Paclitaxel (Day 1) N=20, 0, 0	3.35 µg/mL Geometric Coefficient of Variation 23	NA µg/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA µg/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of Paclitaxel (Day 43) N=14, 0, 0	3.19 µg/mL Geometric Coefficient of Variation 26	NA µg/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA µg/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of Dacarbazine (Day 1) N=0, 19, 0	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	18.23 µg/mL Geometric Coefficient of Variation 37	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of Dacarbazine (Day 43) N=0, 16, 0	NA µg/mL Geometric Coefficient of Variation NA .Dacarbazine not administered in this arm	18.61 µg/mL Geometric Coefficient of Variation 30	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of AIC (Day 1) N=0, 19, 0	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	3.57 µg/mL Geometric Coefficient of Variation 36	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population Cmax of AIC (Day 43) N=0, 17, 0	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	3.98 µg/mL Geometric Coefficient of Variation 40	NA µg/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm

PRIMARY outcome

Timeframe: Day 1 (0 h) to Day 43

Population: N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

AUC=micrograms\*hour(h) per mL (µg\*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(0-21d) of Ipilimumab N=14, 14, 12	46925.36 µg*h/mL Geometric Coefficient of Variation 36	49569.06 µg*h/mL Geometric Coefficient of Variation 25	54039.79 µg*h/mL Geometric Coefficient of Variation 28
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of Paclitaxel (Day 1) N=20, 0, 0	12.37 µg*h/mL Geometric Coefficient of Variation 24	NA µg*h/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA µg*h/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of Paclitaxel (Day 43) N=14, 0, 0	13.41 µg*h/mL Geometric Coefficient of Variation 24	NA µg*h/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA µg*h/mL Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of Dacarbazine (Day 1) N=0, 19, 0	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	47.36 µg*h/mL Geometric Coefficient of Variation 68	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of Dacarbazine (Day 43) N=0, 16, 0	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	41.13 µg*h/mL Geometric Coefficient of Variation 55	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of AIC (Day 1) N=0, 18, 0	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	17.68 µg*h/mL Geometric Coefficient of Variation 26	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.
Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population AUC(INF) of AIC (Day 43) N=0, 16, 0	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	17.38 µg*h/mL Geometric Coefficient of Variation 36	NA µg*h/mL Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.

SECONDARY outcome

Timeframe: Day 1 (0 h) to Day 43

Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of Ipilimumab N=14, 14, 12	1.51 h Interval 1.5 to 24.0	4.00 h Interval 1.5 to 24.6	1.56 h Interval 1.5 to 4.0
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of Paclitaxel (Day 1) N=20, 0, 0	3.00 h Interval 2.9 to 4.3	NA h Paclitaxel not administered in this arm.	NA h Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of Paclitaxel (Day 43) N=14, 0, 0	3.00 h Interval 1.5 to 9.5	NA h Paclitaxel not administered in this arm.	NA h Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of Dacarbazine (Day 1) N=0, 18, 0	NA h Dacarbazine not administered in this arm	1.00 h Interval 1.0 to 2.8	NA h Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of Dacarbazine (Day 43) N=0, 15, 0	NA h Dacarbazine not administered in this arm	1.00 h Interval 1.0 to 1.1	NA h Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of AIC (Day 1) N=0, 19 0	NA h Dacarbazine not administered in this arm	1.00 h Interval 1.0 to 2.8	NA h Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Tmax of AIC (Day 43) N=0, 16, 0	NA h Dacarbazine not administered in this arm	1.00 h Interval 1.0 to 2.5	NA h Dacarbazine not administered in this arm

SECONDARY outcome

Timeframe: Day 1 (0 h) to Day 43

T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of Ipilimumab N=14, 14, 12	13.93 h Standard Deviation 7.54	13.39 h Standard Deviation 4.51	15.25 h Standard Deviation 4.64
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of Paclitaxel (Day 1) N=20, 0, 0	10.26 h Standard Deviation 1.57	NA h Standard Deviation NA Paclitaxel not administered in this arm.	NA h Standard Deviation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of Paclitaxel (Day 43) N=14, 0, 0	10.41 h Standard Deviation 2.73	NA h Standard Deviation NA Paclitaxel not administered in this arm.	NA h Standard Deviation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of Dacarbazine (Day 1) N=0, 19, 0	NA h Standard Deviation NA Dacarbazine not administered in this arm	2.11 h Standard Deviation 0.87	NA h Standard Deviation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of Dacarbazine (Day 43) N=0, 16, 0	NA h Standard Deviation NA Dacarbazine not administered in this arm	2.07 h Standard Deviation 0.85	NA h Standard Deviation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of AIC (Day 1) N=0, 18, 0	NA h Standard Deviation NA Dacarbazine not administered in this arm	2.24 h Standard Deviation 0.96	NA h Standard Deviation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population T(HALF) of AIC (Day 43) N=0, 16, 0	NA h Standard Deviation NA Dacarbazine not administered in this arm	2.21 h Standard Deviation 0.81	NA h Standard Deviation NA Dacarbazine not administered in this arm

SECONDARY outcome

Timeframe: Day 1 (0 h) to Day 43

CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of AIC (Day 43) N=0, 17, 0	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	88.75 mL/h Geometric Coefficient of Variation 37	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of Ipilimumab N=14, 14, 12	11.63 mL/h Geometric Coefficient of Variation 50	11.17 mL/h Geometric Coefficient of Variation 34	10.23 mL/h Geometric Coefficient of Variation 44
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of Paclitaxel (Day 1) N=20, 0, 0	27.87 mL/h Geometric Coefficient of Variation 28	NA mL/h Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA mL/h Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of Paclitaxel (Day 43) N=14, 0, 0	25.44 mL/h Geometric Coefficient of Variation 26	NA mL/h Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA mL/h Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of Dacarbazine (Day 1) N=0, 19, 0	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	34.33 mL/h Geometric Coefficient of Variation 52	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of Dacarbazine (Day 43) N=0, 16, 0	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	37.09 mL/h Geometric Coefficient of Variation 49	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population CLT of AIC (Day 1) N=0, 19, 0	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm	91.67 mL/h Geometric Coefficient of Variation 28	NA mL/h Geometric Coefficient of Variation NA Dacarbazine not administered in this arm

SECONDARY outcome

Timeframe: Day 1 (0 h) to Day 43

Population: N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=12 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Vss of Ipilimumab N=14, 14, 12	5.10 L Geometric Coefficient of Variation 25	4.88 L Geometric Coefficient of Variation 21	5.05 L Geometric Coefficient of Variation 29
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Vss of Dacarbazine (Day 43) N=0, 16, 0	NA L Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	107.90 L Geometric Coefficient of Variation 31	NA L Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Vss of AIC (Day 1) N=0, 17, 0	NA L Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.	342.64 L Geometric Coefficient of Variation 47	NA L Geometric Coefficient of Variation NA Dacarbazine not administered in this arm.
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population Vss of Paclitaxel (Day 43) N=14, 0, 0	205.63 L Geometric Coefficient of Variation 31	NA L Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.	NA L Geometric Coefficient of Variation NA Paclitaxel not administered in this arm.

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants Complete Response	1 participants	1 participants	0 participants
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants Partial Response	1 participants	4 participants	5 participants
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants Stable Disease	6 participants	5 participants	4 participants
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants Progressive Disease	9 participants	8 participants	8 participants
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants Unknown	3 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants ir Partial Response	4 participants	5 participants	5 participants
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants ir Stable Disease	5 participants	5 participants	6 participants
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants ir Progressive Disease	7 participants	7 participants	6 participants
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants ir Unknown	3 participants	1 participants	3 participants
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants ir Complete Response	1 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Randomized Population includes all participants randomized to a treatment arm

Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants Participants with Objective Response	2 participants	5 participants	5 participants
Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants Participants with Disease Control	8 participants	10 participants	9 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Participants with SAEs	9 participants	8 participants	9 participants
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Deaths	12 participants	5 participants	7 participants
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Participants with AEs	20 participants	19 participants	20 participants
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Participants with SAEs Treatment-Related	4 participants	6 participants	5 participants
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Deaths Treatment-Related	0 participants	0 participants	0 participants
Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population Participants discontinued due to AE(s)	6 participants	7 participants	5 participants

SECONDARY outcome

Timeframe: Day to Week 12

Population: Pharmacodynamic Population: All treated participants with one unambiguous date of first dose; and at least 1 ALC evaluation during the induction-dosing period. For each of these participants, all ALC evaluations from 28 days prior to first dose of any study medication to the end of the induction dosing are included. period.

Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number\*10\^3 cells per micro liter (x10\^3 c/µL).

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=29 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population Nominal Ipilimumab Induction Dose Number 4	1.42 10^3 cells/µL Interval 1.03 to 1.8	1.87 10^3 cells/µL Interval 1.49 to 2.25	1.80 10^3 cells/µL Interval 1.39 to 2.22
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population End of Ipilimumab Induction dosing Period	1.67 10^3 cells/µL Interval 1.23 to 2.1	2.07 10^3 cells/µL Interval 1.63 to 2.51	1.73 10^3 cells/µL Interval 1.2 to 2.25
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population Nominal Ipilimumab Induction Dose Number 1	1.19 10^3 cells/µL Interval 0.79 to 1.59	1.41 10^3 cells/µL Interval 1.0 to 1.82	1.28 10^3 cells/µL Interval 0.91 to 1.64
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population Nominal Ipilimumab Induction Dose Number 2	1.62 10^3 cells/µL Interval 1.27 to 1.98	2.05 10^3 cells/µL Interval 1.69 to 2.42	1.56 10^3 cells/µL Interval 1.18 to 1.93
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population Nominal Ipilimumab Induction Dose Number 3	1.43 10^3 cells/µL Interval 1.06 to 1.8	1.96 10^3 cells/µL Interval 1.59 to 2.33	1.99 10^3 cells/µL Interval 1.59 to 2.39

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug. N=number of treated participants who also had blood pressure value available for analysis.

Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=1 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=6 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=9 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population Systolic Blood Pressure at Week 48 (N=1, 4, 4)	5.0 mmHg Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	1.0 mmHg Standard Deviation 17.1	12.0 mmHg Standard Deviation 8.6
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population Diastolic Blood Pressure at Week 48 (N=1, 4, 4)	2.0 mmHg Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	7.0 mmHg Standard Deviation 11.3	8.5 mmHg Standard Deviation 8.2
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population Systolic Blood Pressure at Week 16 (N=1, 6, 9)	22.0 mmHg Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	2.7 mmHg Standard Deviation 12.2	9.7 mmHg Standard Deviation 14.1
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population Diastolic Blood Pressure at Week 16 (N=1, 6, 9)	10.0 mmHg Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	6.6 mmHg Standard Deviation 11.3	4.9 mmHg Standard Deviation 13.3

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Pulse rate value available for analysis.

Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=1 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=6 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=9 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population Pulse Rate at Week 16 (N=1, 6, 9)	24.0 bpm Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	0.3 bpm Standard Deviation 13.9	-0.7 bpm Standard Deviation 15.9
Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population Pulse Rate at Week 48 (N=1, 4, 4)	-3.0 bpm Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	-9.5 bpm Standard Deviation 13.6	7.5 bpm Standard Deviation 10.3

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Respiration rate value available for analysis.

Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=1 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=5 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=6 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population Respiration Rate at Week 16 (N=1, 5, 6)	0 bpm Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation	1.4 bpm Standard Deviation 2.4	-0.8 bpm Standard Deviation 2.2
Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population Respiration Rate at Week 48 (N=1, 3, 3)	-2.0 bpm Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation	-2.7 bpm Standard Deviation 1.2	-1.3 bpm Standard Deviation 1.2

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug. N=number of treated participants who also had a temperature value available for analysis.

Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population Temperature at Week 16 (N=1, 6, 9)	-0.5 degrees F Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	-0.1 degrees F Standard Deviation 0.8	0.2 degrees F Standard Deviation 0.9
Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population Temperature at Week 48 (N=1, 4, 4)	0.4 degrees F Standard Deviation NA N=1 so since only 1 participant was analyzed there can be no standard deviation.	0.0 degrees F Standard Deviation 0.7	-0.2 degrees F Standard Deviation 0.7

SECONDARY outcome

Timeframe: Day 1 to Week 48

Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (\<) lower limit of normal (LLN); GRADE (2): 8.0 - \< 10.0; GRADE (3): 6.5 - \< 8.0; GRADE (4): \< 6.5

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population Hemoglobin Grade 0	3 participants	4 participants	5 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population Hemoglobin Grade 1	9 participants	13 participants	10 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population Hemoglobin Grade 2	8 participants	1 participants	4 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population Hemoglobin Grade 3	0 participants	1 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population Hemoglobin Not Reported	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Leukocytes are measured as \*10\^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - \< LLN; GRADE (2): 2.0 - \< 3.0; GRADE (3): 1.0 - \< 2.0; GRADE (4): \< 1.0.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Grade 0	8 participants	13 participants	17 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Grade 1	4 participants	4 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Grade 2	2 participants	2 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Grade 3	5 participants	0 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Grade 4	1 participants	0 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population Leukocytes Not Reported	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Lymphocytes (absolute) were measured as \*10\^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - \< 1.5; GRADE (2): 0.5 - \< 0.8; GRADE (3): 0.2 - \< 0.5; GRADE (4): \< 0.2

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population Lymphocytes Grade 1	12 participants	13 participants	11 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population Lymphocytes Grade 2	3 participants	1 participants	3 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population Lymphocytes Grade 3	1 participants	0 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population Lymphocytes Grade 0	4 participants	5 participants	6 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Neutrophils (absolute) are measured as \*10\^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - \< 2.0; GRADE (2): 1.0 - \< 1.5; GRADE (3): 0.5 - \< 1.0; GRADE (4): \< 0.5

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population Neutrophils Grade 0	20 participants	18 participants	19 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population Neutrophils Grade 1	0 participants	0 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population Neutrophils Grade 3	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Neutrophils plus bands (absolute) were measured as \*10\^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - \< 2.0; GRADE (2): 1.0 - \< 1.5; GRADE (3): 0.5 - \< 1.0; GRADE (4): \< 0.5.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population Neutrophils Plus Bands Grade 0	20 participants	18 participants	19 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population Neutrophils Plus Bands Grade 1	0 participants	0 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population Neutrophils Plus Bands Grade 3	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Platelets were measured as \*10\^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - \< LLN; GRADE (2): 50.0 - \< 75.0; GRADE (3): 25.0 - \< 50.0; GRADE (4): \< 25.0.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population Platelet Count Grade 0	20 participants	19 participants	18 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population Platelet Count Grade 1	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 2.5 \* upper limits of normal (ULN); GRADE (2): \> 2.5 - 5.0 \* ULN; GRADE (3): \> 5.0 - 20.0 \* ULN; GRADE (4): \> 20.0 \* ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population ALT Grade 0	18 participants	18 participants	16 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population ALT Grade 1	2 participants	1 participants	3 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population ALT Grade 2	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 2.5 \* upper limits of normal (ULN); GRADE (2): \> 2.5 - 5.0 \* ULN; GRADE (3): \> 5.0 - 20.0 \* ULN; GRADE (4): \> 20.0 \* ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population AST Grade 0	18 participants	18 participants	15 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population AST Grade 1	2 participants	1 participants	4 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population AST Grade 2	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \< LLN - 3.0; GRADE (2): \< 3.0 - 2.0; GRADE (3): \< 2.0 g/dL.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population Albumin Grade 0	17 participants	14 participants	14 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population Albumin Grade 1	3 participants	5 participants	6 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 2.5 \* upper limits of normal (ULN); GRADE (2): \> 2.5 - 5.0 \* ULN; GRADE (3): \> 5.0 - 20.0 \* ULN; GRADE (4): \> 20.0 \* ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population Alkaline Phosphatase Grade 0	14 participants	18 participants	18 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population Alkaline Phosphatase Grade 1	6 participants	1 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population Alkaline Phosphatase Grade 2	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 1.5 \* upper limits of normal (ULN); GRADE (2): \> 1.5 - 3.0 \* ULN; GRADE (3): \> 3.0 - 10.0 \* ULN; GRADE (4): \> 10.0 \* ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population Total Bilirubin Grade 0	20 participants	17 participants	18 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population Total Bilirubin Grade 1	0 participants	1 participants	2 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population Total Bilirubin Grade 2	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - \< LLN OR \> ULN - 5.5;; GRADE (2): \> 5.5 - 6.0; GRADE (3): 2.5 - \< 3.0 \> 6.0 - 7.0; GRADE (4): \< 2.5 mEq/L.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population Serum Potassium (High) Grade 0	20 participants	17 participants	17 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population Serum Potassium (High) Grade 1	0 participants	2 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population Serum Potassium (High) Grade 2	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 1.5 \* upper limits of normal (ULN); GRADE (2): \> 1.5 - 2.0 \* ULN; GRADE (3): \> 2.0 - 5.0 \* ULN; GRADE (4): \> 5.0 \* ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population Total Amylase Grade 0	20 participants	19 participants	16 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population Total Amylase Grade 1	0 participants	0 participants	2 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population Total Amylase Grade 2	0 participants	0 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population Total Amylase Grade 3	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - \< LLN OR \> ULN - 11.5; GRADE (2): 7.0 - \< 8.0 \> 11.5 - 12.5; GRADE (3): 6.0 - \< 7.0 \> 12.5 - 13.5; GRADE (4): \< 6.0 \> 13.5 mg/dL.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population Total Calcium (High) Grade 0	18 participants	19 participants	19 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population Total Calcium (High) Grade 1	2 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 - 1.5 \* ULN; GRADE (2): \> 1.5 - 2.0 \* ULN; GRADE (3): \> 2.0 - 5.0 \* ULN; GRADE (4): \> 5.0 X ULN.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population Total Lipase Grade 0	12 participants	6 participants	4 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population Total Lipase Grade 1	1 participants	0 participants	0 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population Total Lipase Grade 4	0 participants	0 participants	1 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population Total Lipase Not Reported	7 participants	13 participants	15 participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Treated participants received at least one dose of a study drug.

Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): \> 1.0 \* ULN - 10.0; GRADE (4): \> 10.0 mg/dL.

Outcome measures

Outcome measures
Measure	Paclitaxel, Carboplatin, Ipilimumab n=20 Participants Induction Phase: Participant received paclitaxel 175 mg/m\^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Dacarbazine, Ipilimumab n=19 Participants Induction Phase: Participant received dacarbazine 850 mg/m\^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Ipilimumab n=20 Participants Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population Uric Acid Grade 0	20 participants	19 participants	17 participants
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population Uric Acid Grade 1	0 participants	1 participants	3 participants

Adverse Events

Paclitaxel, Carboplatin, Ipilimumab

Serious events: 12 serious events

Other events: 20 other events

Deaths: 0 deaths

Dacarbazine, Ipilimumab

Serious events: 10 serious events

Other events: 19 other events

Deaths: 0 deaths

Ipilimumab

Serious events: 14 serious events

Other events: 20 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 Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER