Non-Small Cell Lung Cancer
Conditions
Brief summary
The primary purpose of this study was to establish the recommended dose of ipilimumab administered in combination with paclitaxel and carboplatin in Japanese patients with nonsmall-cell lung cancer.
Interventions
DRUGIpilimumab, 3 mg
Intervenous (IV) injection, administered every 3 weeks for up to 6 cycles
DRUGIpilimumab, 10 mg
IV injection, administered every 3 weeks for up to 6 cycles
DRUGPaclitaxel
IV injection, 175 mg/m\^2, administered every 3 weeks for up to 6 cycles
DRUGCarboplatin
IV injection, AUC=6, administered every 3 weeks for up to 6 cycles. (AUC=area under the concentration curve)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically or cytologically documented nonsmall-cell lung cancer (NSCLC) presenting as stage IIIB disease without indications for definitive radiotherapy, stage IV disease, or recurrent disease following radiation therapy or surgical resection * No prior chemotherapy, hormonal therapy, immunotherapy, or targeted-therapy-containing regimens for the treatment of NSCLC * Life expectancy of at least 3 months * Eastern Cooperative Oncology Group performance score of 0-1 * Adequate bone marrow function * Hemoglobin ≥9.0 g/dL * Absolute neutrophil count ≥1,500/mm\^3 * Platelet count ≥100,000/mm\^3 * Adequate liver function * Total bilirubin level ≤2.0\*the upper limit of normal (ULN) * Asparate aminotransferase level ≤2.5\*ULN * Alanine aminotransferase level ≤2.5\*ULN * Adequate renal function * Calculated creatinine clearance based on Cockcroft and Gault formula ≥50 mL/min. Key
Exclusion criteria
* Symptomatic central nervous system (CNS) metastasis or active CNS metastasis requiring medication * Malignant body cavity fluid (eg, pleural effusion, cardiac effusion, ascites) that recurred despite appropriate supportive care * Prior radiation of ≥30% of major bone-marrow containing areas (pelvis, lumbar spine) * Documented history of severe autoimmune or immune-mediated symptomatic disease that required prolonged (longer than 2 months) systemic immunosuppressant treatment * Documented history of motor neuropathy considered of autoimmune origin (eg, Guillain Barré syndrome) * Any concurrent malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, carcinoma of the mucous membrane of the gastrointestinal tract, or superficial bladder cancer treated with systemic therapy * ≥Grade 2 diarrhea * History of or concurrent disease of gastrointestinal tract perforations * ≥Grade 2 peripheral neuropathy (motor or sensory) * Uncontrolled intercurrent illness including infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, and cardiac arrhythmia requiring medication * Positive finding for human immunodeficiency virus antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease | Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6 | 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. |
| Maximum Serum Concentration (Cmax) of Ipilimumab | During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose 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. |
| Trough Observed Serum Concentration (Cmin) of Ipilimumab | During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose 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. |
| 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 | Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of 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). |
| Time of Maximum Observed Serum Concentration (Tmax) | During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose 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. |
| Serum Half-life (T-HALF) of Ipilimumab | During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose 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. |
| Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab | During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose 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. |
Countries
Japan
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 8 |
| 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). | 7 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Disease progression | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Total |
|---|---|---|---|
| Age, Continuous | 56.0 Years STANDARD_DEVIATION 12.62 | 58.9 Years STANDARD_DEVIATION 10.25 | 57.3 Years STANDARD_DEVIATION 11.26 |
| Age, Customized 65 years and older | 1 Participants | 3 Participants | 4 Participants |
| Age, Customized Younger than 65 years | 7 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Japanese | 8 Participants | 7 Participants | 15 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 7 |
| serious Total, serious adverse events | 3 / 8 | 1 / 7 |
Outcome results
Primary
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
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).
Time frame: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | 2 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | 1 Participants |
Secondary
Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for 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.
Time frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab | 36489 ug*h/mL | Geometric Coefficient of Variation 21 |
Secondary
Maximum Serum Concentration (Cmax) 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.
Time frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Maximum Serum Concentration (Cmax) of Ipilimumab | 72.8 ug/mL | Geometric Coefficient of Variation 12 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Maximum Serum Concentration (Cmax) of Ipilimumab | 201 ug/mL | Geometric Coefficient of Variation 21 |
Secondary
Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
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.
Time frame: Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6
Population: Participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease | PR | 3 Participants |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease | Stable disease | 3 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease | PR | 3 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease | Stable disease | 4 Participants |
Secondary
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
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).
Time frame: Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug
Population: Participants who received at least 1 dose of any study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 | 3 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 | 7 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 | 1 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 | 3 Participants |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | 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 | 1 Participants |
Secondary
Serum Half-life (T-HALF) 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.
Time frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Serum Half-life (T-HALF) of Ipilimumab | 13.3 Days | Standard Deviation 3.64 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Serum Half-life (T-HALF) of Ipilimumab | 11.3 Days | Standard Deviation 2.83 |
Secondary
Time of Maximum Observed Serum Concentration (Tmax)
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.
Time frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Time of Maximum Observed Serum Concentration (Tmax) | 2.75 Hours |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Time of Maximum Observed Serum Concentration (Tmax) | 3.98 Hours |
Secondary
Trough Observed Serum Concentration (Cmin) 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.
Time frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Population: Participants who received at least 1 dose of ipilimumab
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 22 | 11.06 ug/mL | Standard Deviation 1.007 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 43 (n=3, 5) | 10.98 ug/mL | Standard Deviation 4.773 |
| Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 64 (n=3, 3) | 13.90 ug/mL | Standard Deviation 2.6 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 64 (n=3, 3) | 26.40 ug/mL | Standard Deviation 7.904 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 22 | 26.65 ug/mL | Standard Deviation 4.599 |
| Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin | Trough Observed Serum Concentration (Cmin) of Ipilimumab | Day 43 (n=3, 5) | 26.68 ug/mL | Standard Deviation 14.247 |