Trial Outcomes & Findings for Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer (NCT NCT01165216)
NCT ID: NCT01165216
Last Updated: 2014-07-22
Results Overview
A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (\<500 cells/ mm\^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC \<1000 /mm\^3) lasting \>3 days; Grade 4 platelet count decreased (\<25,000 cells/mm\^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels).
COMPLETED
PHASE1
15 participants
Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
2014-07-22
Participant Flow
Participants were enrolled in successive cohorts of 3 to 6 patients, using a standard 3+3 design. Of 15 patients enrolled, all received some treatment (chemotherapy or ipilimumab); 12 received at least 1 dose of ipilimumab.
Participant milestones
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
7
|
|
Overall Study
Received at Least 1 Dose of Ipilimumab
|
6
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
8
|
7
|
Reasons for withdrawal
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Overall Study
Adverse Event
|
6
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Disease progression
|
1
|
3
|
Baseline Characteristics
Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=8 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=7 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.0 Years
STANDARD_DEVIATION 12.62 • n=5 Participants
|
58.9 Years
STANDARD_DEVIATION 10.25 • n=7 Participants
|
57.3 Years
STANDARD_DEVIATION 11.26 • n=5 Participants
|
|
Age, Customized
Younger than 65 years
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Customized
65 years and older
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4Population: Participants who received at least 1 dose of ipilimumab
A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (\<500 cells/ mm\^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC \<1000 /mm\^3) lasting \>3 days; Grade 4 platelet count decreased (\<25,000 cells/mm\^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels).
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drugPopulation: Participants who received at least 1 dose of any study drug
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. AE incidence was assessed from Day 1 until Week 24 and every 12 weeks thereafter during the maintenance period, until discontinuation of study drug, due to progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure, and at least every 4 weeks(±1 week) until all study drug-related toxicities had recovered to resolved, stabilized or returned to baseline or were deemed irreversible during the follow-up period).
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=8 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=7 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
Deaths
|
0 Participants
|
0 Participants
|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
SAEs
|
3 Participants
|
1 Participants
|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
Drug-related SAEs
|
3 Participants
|
1 Participants
|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
Drug-related AEs
|
8 Participants
|
7 Participants
|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
AEs leading to discontinuation
|
6 Participants
|
3 Participants
|
|
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
Drug-related AEs leading to discontinuation
|
6 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6Population: Participants who received at least 1 dose of study drug
Tumor response was determined for all participants with measurable lesions by radiologic responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The BOR was the best response recorded from start of treatment until disease progression/recurrence. RECIST for target lesions: PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. At minimum, tumor measurements were to be obtained at screening, every 6 weeks (±1 week) during the induction phase and every 12 weeks (±1 week) during the maintenance phase.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=8 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=7 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
PR
|
3 Participants
|
3 Participants
|
|
Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
Stable disease
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumabPopulation: Participants who received at least 1 dose of ipilimumab
Cmax was recorded directly from experimental observations. Actual times were used for the analyses. Cmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) of Ipilimumab
|
72.8 ug/mL
Geometric Coefficient of Variation 12
|
201 ug/mL
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumabPopulation: Participants who received at least 1 dose of ipilimumab
Cmin was recorded directly from experimental observations. Actual times were used for the analyses. Cmin measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 (Day 8), and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Trough Observed Serum Concentration (Cmin) of Ipilimumab
Day 22
|
11.06 ug/mL
Standard Deviation 1.007
|
26.65 ug/mL
Standard Deviation 4.599
|
|
Trough Observed Serum Concentration (Cmin) of Ipilimumab
Day 43 (n=3, 5)
|
10.98 ug/mL
Standard Deviation 4.773
|
26.68 ug/mL
Standard Deviation 14.247
|
|
Trough Observed Serum Concentration (Cmin) of Ipilimumab
Day 64 (n=3, 3)
|
13.90 ug/mL
Standard Deviation 2.600
|
26.40 ug/mL
Standard Deviation 7.904
|
SECONDARY outcome
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumabPopulation: Participants who received at least 1 dose of ipilimumab
The AUC(0-21d) was calculated using a mixture of log- and linear-trapezoidal summations. Using no weighting factor, the terminal log-liner phase of the concentration-time curve was determined by least-square linear regression of at least 3 data points. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods using a validated PK analysis program. Actual times were used for the analyses. AUC(0-21d) measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab
|
12632 ug*h/mL
Geometric Coefficient of Variation 12
|
36489 ug*h/mL
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumabPopulation: Participants who received at least 1 dose of ipilimumab
Tmax was recorded directly from experimental observations. Actual times were used for the analyses. Tmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Time of Maximum Observed Serum Concentration (Tmax)
|
2.75 Hours
Interval 1.37 to 4.08
|
3.98 Hours
Interval 1.45 to 23.8
|
SECONDARY outcome
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumabPopulation: Participants who received at least 1 dose of ipilimumab
T-HALF was calculated as the ratio of ln(2) to elimination rate constant (K), where K was estimated as negative slope obtained by regression of the terminal log-linear portion of the serum concentration vs time profile following the ipilimumab dose on Day 1 of Cycle 3. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods, using a validated PK analysis program. Actual times were used for the analyses. T-HALF measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
Outcome measures
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=6 Participants
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses) and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Serum Half-life (T-HALF) of Ipilimumab
|
13.3 Days
Standard Deviation 3.64
|
11.3 Days
Standard Deviation 2.83
|
Adverse Events
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Serious adverse events
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=8 participants at risk
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=7 participants at risk
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyponatraemia
|
12.5%
1/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
12.5%
1/8
|
0.00%
0/7
|
|
Endocrine disorders
Hypoparathyroidism
|
12.5%
1/8
|
0.00%
0/7
|
|
Endocrine disorders
Adrenal insufficiency
|
12.5%
1/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/8
|
14.3%
1/7
|
Other adverse events
| Measure |
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
n=8 participants at risk
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the concentration curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
n=7 participants at risk
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2, administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
|
|---|---|---|
|
Investigations
Blood bilirubin increased
|
0.00%
0/8
|
14.3%
1/7
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/8
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
2/8
|
28.6%
2/7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
2/8
|
0.00%
0/7
|
|
Eye disorders
Eye inflammation
|
12.5%
1/8
|
0.00%
0/7
|
|
Vascular disorders
Flushing
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/8
|
57.1%
4/7
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
12.5%
1/8
|
0.00%
0/7
|
|
Nervous system disorders
Headache
|
12.5%
1/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/8
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
62.5%
5/8
|
28.6%
2/7
|
|
Blood and lymphatic system disorders
Neutropenia
|
87.5%
7/8
|
100.0%
7/7
|
|
Gastrointestinal disorders
Stomatitis
|
25.0%
2/8
|
14.3%
1/7
|
|
Infections and infestations
Tinea pedis
|
12.5%
1/8
|
0.00%
0/7
|
|
Eye disorders
Vitreous floaters
|
12.5%
1/8
|
0.00%
0/7
|
|
Eye disorders
Conjunctivitis
|
12.5%
1/8
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
12.5%
1/8
|
14.3%
1/7
|
|
General disorders
Injection site erythema
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Nausea
|
62.5%
5/8
|
57.1%
4/7
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
25.0%
2/8
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
1/8
|
0.00%
0/7
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/8
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
75.0%
6/8
|
100.0%
7/7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
100.0%
8/8
|
85.7%
6/7
|
|
Investigations
Blood corticotrophin decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Nervous system disorders
Dysgeusia
|
25.0%
2/8
|
14.3%
1/7
|
|
Eye disorders
Eyelid oedema
|
12.5%
1/8
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
12.5%
1/8
|
0.00%
0/7
|
|
Renal and urinary disorders
Haematuria
|
12.5%
1/8
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
12.5%
1/8
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
12.5%
1/8
|
0.00%
0/7
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
12.5%
1/8
|
0.00%
0/7
|
|
Investigations
Weight decreased
|
50.0%
4/8
|
42.9%
3/7
|
|
Investigations
Weight increased
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
Blood pressure decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
Blood sodium decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Infections and infestations
Bronchitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/8
|
28.6%
2/7
|
|
Gastrointestinal disorders
Gastritis
|
12.5%
1/8
|
0.00%
0/7
|
|
Vascular disorders
Hypertension
|
0.00%
0/8
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/8
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/8
|
14.3%
1/7
|
|
General disorders
Hypothermia
|
12.5%
1/8
|
0.00%
0/7
|
|
General disorders
Injection site pain
|
25.0%
2/8
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
12.5%
1/8
|
0.00%
0/7
|
|
Nervous system disorders
Peripheral motor neuropathy
|
12.5%
1/8
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
1/8
|
57.1%
4/7
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
12.5%
1/8
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
1/8
|
28.6%
2/7
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
Blood magnesium decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/8
|
14.3%
1/7
|
|
Nervous system disorders
Dizziness postural
|
12.5%
1/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
12.5%
1/8
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/8
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
Lymphopenia
|
25.0%
2/8
|
0.00%
0/7
|
|
Reproductive system and breast disorders
Metrorrhagia
|
12.5%
1/8
|
0.00%
0/7
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
87.5%
7/8
|
85.7%
6/7
|
|
General disorders
Pyrexia
|
37.5%
3/8
|
42.9%
3/7
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/8
|
28.6%
2/7
|
|
Nervous system disorders
Somnolence
|
12.5%
1/8
|
0.00%
0/7
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/8
|
14.3%
1/7
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/8
|
14.3%
1/7
|
|
Infections and infestations
Urinary tract infection
|
12.5%
1/8
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/8
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8
|
0.00%
0/7
|
|
Investigations
Blood cortisol decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Infections and infestations
Cystitis
|
12.5%
1/8
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Decreased appetite
|
87.5%
7/8
|
85.7%
6/7
|
|
Gastrointestinal disorders
Dental caries
|
12.5%
1/8
|
0.00%
0/7
|
|
Cardiac disorders
Palpitations
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Tongue coated
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/8
|
14.3%
1/7
|
|
Endocrine disorders
Adrenal insufficiency
|
12.5%
1/8
|
0.00%
0/7
|
|
Investigations
Amylase increased
|
25.0%
2/8
|
28.6%
2/7
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
0.00%
0/8
|
14.3%
1/7
|
|
Investigations
C-reactive protein increased
|
25.0%
2/8
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/8
|
28.6%
2/7
|
|
Investigations
Electrocardiogram QT prolonged
|
50.0%
4/8
|
28.6%
2/7
|
|
General disorders
Fatigue
|
25.0%
2/8
|
71.4%
5/7
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
12.5%
1/8
|
14.3%
1/7
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/8
|
14.3%
1/7
|
|
Reproductive system and breast disorders
Menorrhagia
|
12.5%
1/8
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Rash
|
75.0%
6/8
|
71.4%
5/7
|
|
Immune system disorders
Seasonal allergy
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Constipation
|
50.0%
4/8
|
71.4%
5/7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Diarrhoea
|
37.5%
3/8
|
28.6%
2/7
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/8
|
14.3%
1/7
|
|
Gastrointestinal disorders
Duodenitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Gastrointestinal disorders
Gastric disorder
|
0.00%
0/8
|
14.3%
1/7
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/8
|
14.3%
1/7
|
|
Nervous system disorders
Hypoaesthesia
|
37.5%
3/8
|
0.00%
0/7
|
|
Psychiatric disorders
Insomnia
|
25.0%
2/8
|
28.6%
2/7
|
|
Blood and lymphatic system disorders
Leukopenia
|
50.0%
4/8
|
28.6%
2/7
|
|
Investigations
Lipase increased
|
0.00%
0/8
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
12.5%
1/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/8
|
14.3%
1/7
|
|
Eye disorders
Retinal haemorrhage
|
12.5%
1/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8
|
28.6%
2/7
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER