CP-751,871 In Combination With Docetaxel In Advance Non-hematologic Malignancies

Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871

The development of HAHA is considered clinically relevant when temporally associated to the onset of adverse events or a significant decrease in the plasma concentrations of CP-751,871. The positive value is defined as ≥3.32.

Time frame: 30 minutes predose at each cycle, End of Study (28 days after the last CP-751,871 infusion), and 150 days after the last CP-751,871 infusion

Number of Participants With Objective Response (OR)

Number of participants with OR 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, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days)

Time to Tumor Progression (TTP)

Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\])

Time frame: Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days)

Circulating Tumor Cells (CTCs), CTCs Expressing Insulin-like Growth Factor 1 Receptor (IGF-1R), and Circulating Endothelial Cells (CECs)

Time frame: Predose on Day 1 and on Day 8 of each cycle, and End of Study (28 days after the last CP-751,871 infusion)

Systemic Clearance (CL) of CP-751,871 in Cycle 1

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Systemic Clearance (CL) of CP-751,871 in Cycle 4

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1

Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 4

Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1

Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 4

Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1

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

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 4

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

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 4

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 1

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Volume of Distribution (Vz) of CP-751,871 in Cycle 1

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 4

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Volume of Distribution (Vz) of CP-751,871 in Cycle 4

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 1

Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle.

Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4

Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle.

Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)

Observed Accumulation Ratio (Rac) of CP-751,871

AUCtao of Cycle 4 divided by AUC(0-d22) of Cycle 1

Time frame: 30 minutes prior to CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of CP-751,871 infusion; and 30 minutes prior to the next cycle CP-751,871 infusion (Day 22) in Cycle 1 and Cycle 4

Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4

Cday22 is the measured CP-751,871 plasma concentration in blood sample collected at Day 22.

Time frame: Cycle 1: 30 minutes prior to the Cycle 2 CP-751,871 infusion (this is Day 22 for Cycle 1); Cycle 4: 30 minutes prior to the Cycle 5 CP-751,871 infusion (this is Day 22 for Cycle 4)

Time of Last Quantifiable Time Point (Tlast) of CP-751,871 in Cycle 1 and Cycle 4

Blood samples were collected at timepoints prespecified in the study protocol. Tlast of CP-751,871 was the last time point when blood sample collected was quantifiable for CP-751,871.

Time frame: Cycle 1 and 4: prior to CP-751,871 infusion, at 1 hour post CP-751,871 infusion, and at 1, 3, 7 days post end of docetaxel infusion