Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Advanced Lung Cancer

A DLT was defined as any one of the following adverse events observed in Cycle 1 which was considered as related to CP-751,871 combination therapy; 1) \>=Grade 3 gastrointestinal toxicity, hyperglycemia and/or fatigue despite the use of adequate/optimal medical intervention, 2) Any other \>=Grade 3 toxicity not classified under CTCAE blood/bone marrow, or 3) Grade 4 neutropenia that persisted for \>=7 consecutive days or was complicated by fever (defined as a body temperature \>38.0 Celsius degree), 4) Grade 3 thrombocytopenia which needed blood transfusion or Grade 4 thrombocytopenia.

Time frame: Cycle 1

Population: DLT Evaluation Set comprised of participants who were treated with CP-751,871. One participant in the 10 mg/kg cohort who discontinued from the study due to an adverse event occurred prior to CP-751,871 administration was excluded from this analysis set.

AUCtau: AUC from time zero to tau, the dosing interval, where tau is the actual time of the predose sampling for the next cycle. AUCtau was calculated using the linear/log trapezoidal method.

Time frame: Cycle 4: prior to CP-751,871 (Day 1) dosing , and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Population: The Pharmacokinetics Analysis Set was defined as all participants who started treatment and had sufficient information for estimation of pharmacokinetic parameters.

AUC(0-day22) : AUC from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sampling for the next cycle. AUC(0-day22) was calculated using the linear/log trapezoidal method.

Time frame: Cycle 1: prior CP-751,871 (Day 1) to dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Population: The Pharmacokinetics Analysis Set was defined as all participants who started treatment and had sufficient information for estimation of pharmacokinetic parameters.

Time frame: Cycles 1 and 4 at prior to dosing of CP-751,871 (Day 1), and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Population: The Pharmacokinetics Analysis Set was defined as all participants who started treatment and had sufficient information for estimation of pharmacokinetic parameters.~n = the number of participants analyzed

Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Time frame: Baseline up to 6 cycles (1 cycle = 21 days)

Population: Full Analysis Set (FAS) was defined as all participants who met all of the following criteria; 1) Those who were diagnosed with NSCLC, 2) Those who received at least one dose of the study treatment, and 3) Those who had efficacy data after the start of the study treatment.

The screening assay for anti-CP-751,871 antibodies was performed.

Time frame: Day 1 of Cycles 1 (predose) and 4, and end of study

Population: All participants were screened for the ADA.

The ratio of Cycle 4 AUCtau to Cycle 1 AUCtau

Time frame: Cycle 1 and Cycle 4: prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Population: The Pharmacokinetics Analysis Set was defined as all participants who started treatment and had sufficient information for estimation of pharmacokinetic parameters.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: Cycle 1 : prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Population: Participants with sufficient sampling to capture the terminal disposition phase were analyzed.

PFS is the period from the registration to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

Time frame: Baseline up to 6 cycles (1 cycle = 21 days)

Population: Number of participants with defined event (all causality death or PD) was too few to conduct summary analysis.

IGF-1 is one of the IGF-axis related biomarkers.

Time frame: Day 1 of Cycles 1 to 6, Day 8 of Cycles 1 to 4, and end of study

Population: Safety Analysis Set was defined as all participants who have received at least one dose of the study medication. n = number of subjects evaluable.

IGF-BP3 is one of the IGF-axis related biomarkers.

Time frame: Day 1 of Cycles 1-6, Day 8 of Cycles 1-4, and end of treatment

Population: Safety Analysis Set was defined as all participants who have received at least one dose of the study medication. n = number of subjects evaluable.