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

A Randomized, Parallel, 3-arm Study to Characterize the Effect of Ipilimumab + Chemotherapy in Patients With Untreated Advanced Melanoma

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00796991

Enrollment

Registered

2008-11-24

Start date

2009-02-28

Completion date

2012-10-31

Last updated

2014-01-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Melanoma

Keywords

Untreated Advanced Melanoma

Brief summary

The purpose of this clinical research study is to learn the pharmacokinetics of Ipilimumab when combined with Paclitaxel/Carboplatin or Dacarbazine

Interventions

DRUGIpilimumab

Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks

DRUGCarboplatin

Solution, intravenous, Area Under the Concentration Time Curve=6, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks

DRUGPaclitaxel

Solution, intravenous, 175 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks

DRUGDacarbazine

Solution, intravenous, 850 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologic diagnosis of advanced malignant melanoma * Eastern Cooperative Oncology Group (ECOG) performances status 0-1 * Measurable/evaluable disease as per modified World Health Organization (mWHO) criteria

Exclusion criteria

* Evidence of active brain metastases * Prior treatment with anti-cytotoxic lymphocyte antigen 4 (CTLA-4) or anti-CD137 (type of tumor necrosis factor) antibody * Total Bilirubin greater than (\>) 1.5 \* upper limit of normal (ULN) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 \* upper limit of normal (ULN) * Prior Autoimmune disease * Use of immunosuppressing therapies

Design outcomes

Primary

Measure	Time frame	Description
Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population	Day 1 (0 h) to Day 43	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.
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	Day 1 (0 h) to Day 43	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.

Secondary

Measure	Time frame	Description
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	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..
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	Day 1 (0 h) to Day 43	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.
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Day 1 to Week 48	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.
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	Day 1 to Week 48	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.
Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Day 1 to Week 48	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.
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	Day 1 to Week 48	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.
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population	Day to Week 12	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).
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population	Day 1 to Week 48	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.
Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population	Day 1 to Week 48	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.
Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population	Day 1 to Week 48	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.
Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population	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
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population	Day 1 to Week 48	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.
Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	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..
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Day 1 to Week 48	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
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population	Day 1 to Week 48	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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population	Day 1 to Week 48	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
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	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.

Countries

United States

Participant flow

Recruitment details

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

Pre-assignment details

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.

Participants by arm

Arm	Count
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.	20
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.	19
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.	20
Total	59

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
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

Characteristic	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	5 Participants	7 Participants	8 Participants	20 Participants
Age, Categorical Between 18 and 65 years	15 Participants	12 Participants	12 Participants	39 Participants
Age, Continuous	55 years STANDARD_DEVIATION 14	54 years STANDARD_DEVIATION 17	60 years STANDARD_DEVIATION 11	57 years STANDARD_DEVIATION 14
Eastern Cooperative Oncology Group (ECOG) 0	14 participants	17 participants	16 participants	47 participants
Eastern Cooperative Oncology Group (ECOG) 1	6 participants	1 participants	4 participants	11 participants
Eastern Cooperative Oncology Group (ECOG) 2	0 participants	0 participants	0 participants	0 participants
Eastern Cooperative Oncology Group (ECOG) Not Reported	0 participants	1 participants	0 participants	1 participants
Number of Target Lesions 1 lesion	4 Participants	3 Participants	4 Participants	11 Participants
Number of Target Lesions 2 lesions	3 Participants	3 Participants	0 Participants	6 Participants
Number of Target Lesions 3 lesions	3 Participants	4 Participants	4 Participants	11 Participants
Number of Target Lesions 4 lesions	0 Participants	2 Participants	5 Participants	7 Participants
Number of Target Lesions >=5 lesions	10 Participants	7 Participants	7 Participants	24 Participants
Region of Enrollment United States	20 participants	19 participants	20 participants	59 participants
Sex: Female, Male Female	7 Participants	6 Participants	8 Participants	21 Participants
Sex: Female, Male Male	13 Participants	13 Participants	12 Participants	38 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	20 / 20	19 / 19	20 / 20
serious Total, serious adverse events	12 / 20	10 / 19	14 / 20

Outcome results

Primary

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=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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	47.36 µg*h/mL	Geometric Coefficient of Variation 68
Dacarbazine, Ipilimumab	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	49569.06 µg*h/mL	Geometric Coefficient of Variation 25
Dacarbazine, Ipilimumab	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	NA µg*h/mL	—
Dacarbazine, Ipilimumab	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	NA µg*h/mL	—
Dacarbazine, Ipilimumab	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	41.13 µg*h/mL	Geometric Coefficient of Variation 55
Dacarbazine, Ipilimumab	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	17.68 µg*h/mL	Geometric Coefficient of Variation 26
Dacarbazine, Ipilimumab	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	17.38 µg*h/mL	Geometric Coefficient of Variation 36
Ipilimumab	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	—
Ipilimumab	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	NA µg*h/mL	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	NA µg*h/mL	—
Ipilimumab	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	54039.79 µg*h/mL	Geometric Coefficient of Variation 28

Comparison: Estimated effect of ipilimumab on paclitaxel AUC(INF). Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the paclitaxel/carboplatin/ipilimumab combination (Day 43) relative to paclitaxel/carboplatin alone (Day 1).90% CI: [0.954, 1.196]Mixed Models Analysis

Comparison: Estimated effect of ipilimumab on dacarbazine AUC(INF). Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).90% CI: [0.757, 1.099]Mixed Models Analysis

Comparison: Estimated effect of ipilimumab on AUC(INF) for AIC. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).90% CI: [0.891, 1.056]Mixed Models Analysis

Comparison: Estimated effect of paclitaxel/carboplatin on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in first and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the 3 drug combination relative to ipilimumab alone.90% CI: [0.768, 1.136]linear model

Comparison: Estimated effect of dacarbazine on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in second and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination relative to ipilimumab alone.90% CI: [0.7981, 1.208]linear model

Primary

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=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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	18.23 µg/mL	Geometric Coefficient of Variation 37
Dacarbazine, Ipilimumab	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	246.50 µg/mL	Geometric Coefficient of Variation 35
Dacarbazine, Ipilimumab	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	NA µg/mL	—
Dacarbazine, Ipilimumab	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	NA µg/mL	—
Dacarbazine, Ipilimumab	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	18.61 µg/mL	Geometric Coefficient of Variation 30
Dacarbazine, Ipilimumab	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	3.57 µg/mL	Geometric Coefficient of Variation 36
Dacarbazine, Ipilimumab	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	3.98 µg/mL	Geometric Coefficient of Variation 40
Ipilimumab	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	—
Ipilimumab	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	NA µg/mL	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	NA µg/mL	—
Ipilimumab	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	251.05 µg/mL	Geometric Coefficient of Variation 34

Comparison: Estimated effect of ipilimumab on paclitaxel Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the paclitaxel/carboplatin/ipilimumab combination (Day 43) relative to paclitaxel/carboplatin alone (Day 1)90% CI: [0.794, 1.168]Mixed Models Analysis

Comparison: Estimated effect of ipilimumab on dacarbazine Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).90% CI: [0.848, 1.243]Mixed Models Analysis

Comparison: Estimated effect of ipilimumab on AIC Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).90% CI: [0.974, 1.15]Mixed Models Analysis

Comparison: Estimated effect of paclitaxel/carboplatin on ipilimumab Cmax: linear model was applied to ipilimumab log(Cmax)) data from Week 7 (Day 43) PK measurements in first and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the 3 drug combination relative to ipilimumab alone.90% CI: [0.768, 1.136]linear model

Comparison: Estimated effect of dacarbazine on ipilimumab Cmax: linear model was applied to ipilimumab log(Cmax) data from Week 7 (Day 43) PK measurements in second and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination relative to ipilimumab alone.90% CI: [0.798, 1.208]linear model

Secondary

Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population

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).

Time frame: 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.

Arm	Measure	Group	Value (MEAN)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	1.41 10^3 cells/µL
Dacarbazine, Ipilimumab	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	2.05 10^3 cells/µL
Dacarbazine, Ipilimumab	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	1.96 10^3 cells/µL
Dacarbazine, Ipilimumab	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	1.87 10^3 cells/µL
Dacarbazine, Ipilimumab	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	2.07 10^3 cells/µL
Ipilimumab	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	1.73 10^3 cells/µL
Ipilimumab	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	1.80 10^3 cells/µL
Ipilimumab	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	1.28 10^3 cells/µL
Ipilimumab	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	1.99 10^3 cells/µL
Ipilimumab	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	1.56 10^3 cells/µL

Comparison: null hypothesis of no mean ALC changes over time in any treatment group. Conditional F-tests were used to test for mean ALC changes over time in each treatment arm and the difference between treatment arms in the pattern of change in ALC over time.p-value: 0.027conditional F test

Comparison: null hypothesis that the pattern of mean ALC values over time is the same in all treatment groups. Test of overall time-by-treatment interaction used an omnibus conditional F-test.p-value: 0.5Omnibus conditional F-test

Comparison: null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.p-value: 0.37conditional F-test

Comparison: null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.p-value: 0.85conditional F-test

Comparison: null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.p-value: 0.22conditional F-test

Secondary

Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Dacarbazine, Ipilimumab	Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population	Temperature at Week 16 (N=1, 6, 9)	-0.1 degrees F	Standard Deviation 0.8
Dacarbazine, Ipilimumab	Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population	Temperature at Week 48 (N=1, 4, 4)	0.0 degrees F	Standard Deviation 0.7
Ipilimumab	Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population	Temperature at Week 16 (N=1, 6, 9)	0.2 degrees F	Standard Deviation 0.9
Ipilimumab	Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population	Temperature at Week 48 (N=1, 4, 4)	-0.2 degrees F	Standard Deviation 0.7

Secondary

Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Dacarbazine, Ipilimumab	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)	1.0 mmHg	Standard Deviation 17.1
Dacarbazine, Ipilimumab	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)	6.6 mmHg	Standard Deviation 11.3
Dacarbazine, Ipilimumab	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)	2.7 mmHg	Standard Deviation 12.2
Dacarbazine, Ipilimumab	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)	7.0 mmHg	Standard Deviation 11.3
Ipilimumab	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)	12.0 mmHg	Standard Deviation 8.6
Ipilimumab	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)	8.5 mmHg	Standard Deviation 8.2
Ipilimumab	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)	9.7 mmHg	Standard Deviation 14.1
Ipilimumab	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)	4.9 mmHg	Standard Deviation 13.3

Secondary

Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Dacarbazine, Ipilimumab	Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population	Pulse Rate at Week 16 (N=1, 6, 9)	0.3 bpm	Standard Deviation 13.9
Dacarbazine, Ipilimumab	Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population	Pulse Rate at Week 48 (N=1, 4, 4)	-9.5 bpm	Standard Deviation 13.6
Ipilimumab	Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population	Pulse Rate at Week 16 (N=1, 6, 9)	-0.7 bpm	Standard Deviation 15.9
Ipilimumab	Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population	Pulse Rate at Week 48 (N=1, 4, 4)	7.5 bpm	Standard Deviation 10.3

Secondary

Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Dacarbazine, Ipilimumab	Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population	Respiration Rate at Week 16 (N=1, 5, 6)	1.4 bpm	Standard Deviation 2.4
Dacarbazine, Ipilimumab	Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population	Respiration Rate at Week 48 (N=1, 3, 3)	-2.7 bpm	Standard Deviation 1.2
Ipilimumab	Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population	Respiration Rate at Week 16 (N=1, 5, 6)	-0.8 bpm	Standard Deviation 2.2
Ipilimumab	Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population	Respiration Rate at Week 48 (N=1, 3, 3)	-1.3 bpm	Standard Deviation 1.2

Secondary

Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Complete Response	1 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Progressive Disease	7 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Stable Disease	5 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Unknown	3 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Partial Response	4 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Unknown	1 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Complete Response	1 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Partial Response	5 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Stable Disease	5 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Progressive Disease	7 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Partial Response	5 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Unknown	3 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Progressive Disease	6 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Complete Response	0 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants	ir Stable Disease	6 participants

Secondary

Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Progressive Disease	9 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Stable Disease	6 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Complete Response	1 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Partial Response	1 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Unknown	3 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Stable Disease	5 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Complete Response	1 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Partial Response	4 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Progressive Disease	8 participants
Dacarbazine, Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Unknown	1 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Unknown	3 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Progressive Disease	8 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Complete Response	0 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Stable Disease	4 participants
Ipilimumab	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants	Partial Response	5 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population

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

Time frame: Day 1 to Week 48

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	1 participants
Dacarbazine, Ipilimumab	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	4 participants
Dacarbazine, Ipilimumab	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	13 participants
Dacarbazine, Ipilimumab	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	1 participants
Dacarbazine, Ipilimumab	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
Ipilimumab	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	1 participants
Ipilimumab	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
Ipilimumab	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	5 participants
Ipilimumab	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	4 participants
Ipilimumab	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	10 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	13 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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	0 participants
Dacarbazine, Ipilimumab	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	0 participants
Dacarbazine, Ipilimumab	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
Ipilimumab	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	1 participants
Ipilimumab	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	1 participants
Ipilimumab	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	0 participants
Ipilimumab	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	1 participants
Ipilimumab	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	17 participants
Ipilimumab	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	0 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population

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

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	0 participants
Dacarbazine, Ipilimumab	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	5 participants
Dacarbazine, Ipilimumab	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	1 participants
Dacarbazine, Ipilimumab	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	13 participants
Ipilimumab	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	0 participants
Ipilimumab	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	11 participants
Ipilimumab	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
Ipilimumab	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	6 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population	ALT Grade 1	1 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population	ALT Grade 0	16 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population	ALT Grade 2	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population	ALT Grade 1	3 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population

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.

Time frame: Day 1 to Week 48

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 0	17 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 1	3 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 0	14 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 1	5 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 0	14 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population	Albumin Grade 1	6 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Alkaline Phosphatase Grade 1	1 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Alkaline Phosphatase Grade 0	18 participants
Dacarbazine, Ipilimumab	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
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Alkaline Phosphatase Grade 0	18 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Alkaline Phosphatase Grade 2	2 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population	Alkaline Phosphatase Grade 1	0 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population

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.

Time frame: Day 1 to Week 48

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population	AST Grade 1	1 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population	AST Grade 0	15 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population	AST Grade 2	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population	AST Grade 1	4 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population

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

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 1	0 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 0	20 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 3	0 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 1	0 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 0	18 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 3	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 0	19 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 3	0 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population	Neutrophils Grade 1	1 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population

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.

Time frame: Day 1 to Week 48

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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	18 participants
Dacarbazine, Ipilimumab	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	1 participants
Ipilimumab	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	19 participants
Ipilimumab	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
Ipilimumab	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	1 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population	Platelet Count Grade 0	19 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population	Platelet Count Grade 0	18 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population	Platelet Count Grade 1	2 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	2 participants
Dacarbazine, Ipilimumab	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	17 participants
Dacarbazine, Ipilimumab	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
Ipilimumab	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	17 participants
Ipilimumab	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	2 participants
Ipilimumab	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	1 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Total Amylase Grade 0	19 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Total Amylase Grade 3	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Total Amylase Grade 1	2 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Total Amylase Grade 2	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population	Total Amylase Grade 0	16 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Total Bilirubin Grade 1	1 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Total Bilirubin Grade 0	17 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Total Bilirubin Grade 2	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Total Bilirubin Grade 0	18 participants
Ipilimumab	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
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population	Total Bilirubin Grade 1	2 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	19 participants
Dacarbazine, Ipilimumab	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	0 participants
Ipilimumab	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	19 participants
Ipilimumab	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	1 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Not Reported	13 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Grade 0	6 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Grade 1	0 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Not Reported	15 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Grade 1	0 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Grade 4	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population	Total Lipase Grade 0	4 participants

Secondary

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population	Uric Acid Grade 0	19 participants
Dacarbazine, Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population	Uric Acid Grade 1	1 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population	Uric Acid Grade 0	17 participants
Ipilimumab	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population	Uric Acid Grade 1	3 participants

Secondary

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

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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)	7 participants
Dacarbazine, Ipilimumab	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	19 participants
Dacarbazine, Ipilimumab	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	5 participants
Dacarbazine, Ipilimumab	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
Dacarbazine, Ipilimumab	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	8 participants
Dacarbazine, Ipilimumab	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	6 participants
Ipilimumab	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
Ipilimumab	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	5 participants
Ipilimumab	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)	5 participants
Ipilimumab	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	7 participants
Ipilimumab	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
Ipilimumab	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

Secondary

Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants

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.

Time frame: Day 1 to Week 48

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

Arm	Measure	Group	Value (NUMBER)
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Objective Response	2 participants
Paclitaxel, Carboplatin, Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Disease Control	8 participants
Dacarbazine, Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Objective Response	5 participants
Dacarbazine, Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Disease Control	10 participants
Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Objective Response	5 participants
Ipilimumab	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants	Participants with Disease Control	9 participants

Secondary

Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

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..

Time frame: Day 1 (0 h) to Day 43

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	34.33 mL/h	Geometric Coefficient of Variation 52
Dacarbazine, Ipilimumab	Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	CLT of Ipilimumab N=14, 14, 12	11.17 mL/h	Geometric Coefficient of Variation 34
Dacarbazine, Ipilimumab	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	NA mL/h	—
Dacarbazine, Ipilimumab	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	NA mL/h	—
Dacarbazine, Ipilimumab	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	37.09 mL/h	Geometric Coefficient of Variation 49
Dacarbazine, Ipilimumab	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	91.67 mL/h	Geometric Coefficient of Variation 28
Dacarbazine, Ipilimumab	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	88.75 mL/h	Geometric Coefficient of Variation 37
Ipilimumab	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	—
Ipilimumab	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	NA mL/h	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	NA mL/h	—
Ipilimumab	Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population	CLT of Ipilimumab N=14, 14, 12	10.23 mL/h	Geometric Coefficient of Variation 44

Secondary

Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

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.

Time frame: Day 1 (0 h) to Day 43

Arm	Measure	Group	Value (MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	2.07 h	Standard Deviation 0.85
Dacarbazine, Ipilimumab	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	NA h	—
Dacarbazine, Ipilimumab	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	2.24 h	Standard Deviation 0.96
Dacarbazine, Ipilimumab	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	NA h	—
Dacarbazine, Ipilimumab	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	2.11 h	Standard Deviation 0.87
Dacarbazine, Ipilimumab	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	2.21 h	Standard Deviation 0.81
Dacarbazine, Ipilimumab	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	13.39 h	Standard Deviation 4.51
Ipilimumab	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	—
Ipilimumab	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	15.25 h	Standard Deviation 4.64
Ipilimumab	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	NA h	—
Ipilimumab	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	NA h	—
Ipilimumab	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	—
Ipilimumab	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	—
Ipilimumab	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	—

Secondary

Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

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..

Time frame: Day 1 (0 h) to Day 43

Arm	Measure	Group	Value (MEDIAN)
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Dacarbazine, Ipilimumab	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	1.00 h
Dacarbazine, Ipilimumab	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	4.00 h
Dacarbazine, Ipilimumab	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	NA h
Dacarbazine, Ipilimumab	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	NA h
Dacarbazine, Ipilimumab	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	1.00 h
Dacarbazine, Ipilimumab	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	1.00 h
Dacarbazine, Ipilimumab	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	1.00 h
Ipilimumab	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
Ipilimumab	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	NA h
Ipilimumab	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
Ipilimumab	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
Ipilimumab	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
Ipilimumab	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	NA h
Ipilimumab	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	1.56 h

Secondary

Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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
Paclitaxel, Carboplatin, Ipilimumab	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	—
Paclitaxel, Carboplatin, Ipilimumab	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	—
Dacarbazine, Ipilimumab	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	342.64 L	Geometric Coefficient of Variation 47
Dacarbazine, Ipilimumab	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	4.88 L	Geometric Coefficient of Variation 21
Dacarbazine, Ipilimumab	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	107.90 L	Geometric Coefficient of Variation 31
Dacarbazine, Ipilimumab	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	NA L	—
Ipilimumab	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	—
Ipilimumab	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	NA L	—
Ipilimumab	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	—
Ipilimumab	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	5.05 L	Geometric Coefficient of Variation 29

Source: ClinicalTrials.gov · Data processed: Feb 22, 2026

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

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Study design

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Exclusion criteria

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Primary

Secondary

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Outcome results

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

Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population

Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population

Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population

Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population

Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population

Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population

Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants

Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population

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

Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants

Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population