Trial Outcomes & Findings for Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Advanced Lung Cancer (NCT NCT00603538)

Last Updated: 2013-04-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

19 participants

Primary outcome timeframe

Cycle 1

Results posted on

2013-04-11

Participant Flow

Participant milestones

Participant milestones
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Overall Study STARTED	6	7	6
Overall Study COMPLETED	3	3	4
Overall Study NOT COMPLETED	3	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Overall Study Adverse Event	0	4	2
Overall Study Objective progression or relapse	3	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=7 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	Total n=19 Participants Total of all reporting groups
Age, Customized 20 to 44 years	0 participants n=5 Participants	5 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Age, Customized 45 to 64 years	4 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Age, Customized >=65 years	2 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	5 participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
ECOG Performance Status Score 0	5 participants n=5 Participants	7 participants n=7 Participants	4 participants n=5 Participants	16 participants n=4 Participants
ECOG Performance Status Score 1	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Number of Participants With Dose Limiting Toxicities (DLT)	1 participants	2 participants	0 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Maximum Observed Concentration (Cmax) of CP-751,871 Cycle 4 (n=4,4,5)	178 mg/L Standard Deviation 35	294 mg/L Standard Deviation 61	550 mg/L Standard Deviation 89
Maximum Observed Concentration (Cmax) of CP-751,871 Cycle 1 (n=6,6,6)	113 mg/L Standard Deviation 16	197 mg/L Standard Deviation 33	485 mg/L Standard Deviation 59

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=4 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=1 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=4 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Plasma Decay Half-Life (t1/2)	264 hours Standard Deviation 38.9	NA hours Standard Deviation NA Mean was not calculated because there was only 1 participant to be analyzed.	248 hours Standard Deviation 30.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Area Under the Plasma Concentration-time Curve From Time 0 to Day 22 (AUC0-day22)	22400 mg*h/L Standard Deviation 4050	36700 mg*h/L Standard Deviation 10400	82700 mg*h/L Standard Deviation 11200

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Area Under the Plasma Concentration Curve From Time Zero to Tau (AUCtau)	NA mg*h/mL Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable AUCtau at Cycle 4.	NA mg*h/mL Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable AUCtau at Cycle 4.	NA mg*h/mL Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable AUCtau at Cycle 4.

SECONDARY outcome

Timeframe: 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.

The ratio of Cycle 4 AUCtau to Cycle 1 AUCtau

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=2 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Observed Accumulation Ratio (Rac)	NA ratio Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable Rac at Cycle 4.	NA ratio Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable Rac at Cycle 4.	NA ratio Standard Deviation NA Mean was not calculated because there were only 2 participants who had estimable Rac at Cycle 4.

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=7 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 1 Day 8 (n=6,6,6)	518.3 ng/L Standard Deviation 199.3	611.7 ng/L Standard Deviation 210.9	493.8 ng/L Standard Deviation 114.6
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 3 Day 1 (n=5,4,6)	649.8 ng/L Standard Deviation 129.8	864.0 ng/L Standard Deviation 134.2	706.0 ng/L Standard Deviation 174.3
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 1 Day 1 (n=6,7,6)	126.2 ng/L Standard Deviation 54.0	167.7 ng/L Standard Deviation 64.2	136.8 ng/L Standard Deviation 45.4
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 2 Day 1 (n=6,5,6)	579.8 ng/L Standard Deviation 172.8	773.6 ng/L Standard Deviation 207.1	649.5 ng/L Standard Deviation 104.8
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 2 Day 8 (n=6,5,6)	709.0 ng/L Standard Deviation 205.4	819.8 ng/L Standard Deviation 214.0	544.7 ng/L Standard Deviation 157.0
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 3 Day 8 (n=5,4,6)	774.2 ng/L Standard Deviation 203.4	765.5 ng/L Standard Deviation 43.6	698.0 ng/L Standard Deviation 97.1
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 4 Day 1 (n=4,4,5)	812.5 ng/L Standard Deviation 299.5	867.3 ng/L Standard Deviation 224.1	634.4 ng/L Standard Deviation 66.7
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 4 Day 8 (n=4,4,5)	784.5 ng/L Standard Deviation 148.5	904.8 ng/L Standard Deviation 207.2	749.0 ng/L Standard Deviation 168.5
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 5 Day 1 (n=2,2,2)	908.0 ng/L Standard Deviation 199.4	788.5 ng/L Standard Deviation 187.4	565.0 ng/L Standard Deviation 97.6
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) Cycle 6 Day 1 (n=2,2,1)	835.0 ng/L Standard Deviation 118.8	927.0 ng/L Standard Deviation 2.8	695.0 ng/L Standard Deviation NA Only one participant was available for analysis
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1) End of treatment (n=5,6,6)	562.8 ng/L Standard Deviation 194.5	830.3 ng/L Standard Deviation 304.9	655.2 ng/L Standard Deviation 136.3

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=7 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 1 Day 1 (n=6,7,6)	2.38 mg/L Standard Deviation 0.82	2.26 mg/L Standard Deviation 0.59	2.55 mg/L Standard Deviation 0.39
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 1 Day 8 (n=6,6,6)	4.35 mg/L Standard Deviation 1.41	4.20 mg/L Standard Deviation 0.67	3.85 mg/L Standard Deviation 0.46
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 2 Day 1 (n=6,5,6)	5.12 mg/L Standard Deviation 1.78	5.68 mg/L Standard Deviation 0.29	5.25 mg/L Standard Deviation 1.93
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 2 Day 8 (n=6,5,6)	6.53 mg/L Standard Deviation 2.26	6.26 mg/L Standard Deviation 1.18	4.63 mg/L Standard Deviation 0.71
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 3 Day 1 (n=5,4,6)	6.08 mg/L Standard Deviation 2.23	6.78 mg/L Standard Deviation 1.44	5.07 mg/L Standard Deviation 1.49
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 3 Day 8 (n=5,4,6)	4.66 mg/L Standard Deviation 1.82	5.93 mg/L Standard Deviation 0.75	5.30 mg/L Standard Deviation 1.04
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 4 Day 1 (n=4,4,5)	5.13 mg/L Standard Deviation 1.36	5.18 mg/L Standard Deviation 1.04	4.32 mg/L Standard Deviation 0.38
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 4 Day 8 (n=4,4,5)	5.10 mg/L Standard Deviation 1.55	4.95 mg/L Standard Deviation 2.12	4.44 mg/L Standard Deviation 0.53
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 5 Day 1 (n=2,2,2)	3.45 mg/L Standard Deviation 1.63	5.35 mg/L Standard Deviation 3.89	3.90 mg/L Standard Deviation 1.27
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) Cycle 6 Day 1 (n=2,2,1)	5.75 mg/L Standard Deviation 1.77	6.85 mg/L Standard Deviation 1.20	3.20 mg/L Standard Deviation NA Only one participant was available for analysis
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3) End of treatment (n=5,6,6)	4.66 mg/L Standard Deviation 0.74	5.93 mg/L Standard Deviation 0.75	4.63 mg/L Standard Deviation 0.80

SECONDARY outcome

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

Population: All participants were screened for the ADA.

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

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=7 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Number of Participants With Positive Anti-Drug Antibody (ADA) Specific to CP-751,871 Following an Intravenous Infusion of CP-751,871.	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 Participants CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Number of Participants With Objective Response Complete Response (CR)	0 participants	0 participants	0 participants
Number of Participants With Objective Response Partial Response (PR)	1 participants	3 participants	3 participants
Number of Participants With Objective Response Objective Response (CR+PR)	1 participants	3 participants	3 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

CP-751,871 6 mg/kg in Combination With Chemotherapy Agents

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

CP-751,871 10 mg/kg in Combination With Chemotherapy Agents

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

CP-751,871 20 mg/kg in Combination With Chemotherapy Agents

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CP-751,871 6 mg/kg in Combination With Chemotherapy Agents n=6 participants at risk CP-751,871 6 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 10 mg/kg in Combination With Chemotherapy Agents n=7 participants at risk CP-751,871 10 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.	CP-751,871 20 mg/kg in Combination With Chemotherapy Agents n=6 participants at risk CP-751,871 20 mg/kg was administered intravenously on Day 1 of each 21-day cycle in combination with following chemotherapy; paclitaxel 200 mg/m\^2 was administered intravenously over 3 hours, then carboplatin AUC 6 was administered intravenously over 30 minutes or longer prior to the CP-751,871 infusion. Study treatment was repeated up to 4 cycles, unless disease progression or unacceptable toxicity was observed, and then up to 6 cycles if the participant showed response or stable disease at the end of Cycle 4 and agreed on additional treatment.
Immune system disorders Hypersensitivity	0.00% 0/6 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.3% 1/7 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/6 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/7 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.7% 1/6 • For serious adverse events, up to 150 days after the last administration of the study drugs The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER