Trial Outcomes & Findings for A Study in Non-Small Cell Lung Cancer (NCT NCT01232452)

NCT ID: NCT01232452

Last Updated: 2019-09-20

Results Overview

PFS was defined as the time from date of randomization until the date of disease progression, or death from any cause, whichever was first. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation for disease progression or death were censored at the date of last tumor assessment. The PFS was estimated following the Kaplan-Meier method.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 172 participants
• Primary outcome timeframe: Randomization Date to Disease Progression or Death From Any Cause Up to 18.3 Months
• Results posted on: 2019-09-20

Participant Flow

Completers are those participants who died or had progressive disease (PD).

Participant milestones

Measure	Pemetrexed + Cisplatin + Cixutumumab Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given intravenously (IV) on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Overall Study STARTED	87	85
Overall Study Received at Least One Dose of Study Drug	85	81
Overall Study COMPLETED	48	46
Overall Study NOT COMPLETED	39	39

Reasons for withdrawal

Measure	Pemetrexed + Cisplatin + Cixutumumab Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given intravenously (IV) on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Overall Study Adverse Event	17	15
Overall Study Withdrawal by Subject	11	8
Overall Study Physician Decision	8	12
Overall Study Protocol entry criterion not met	0	2
Overall Study Sponsor Decision	3	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.

Baseline characteristics by cohort

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Total n=172 Participants Total of all reporting groups
Region of Enrollment Netherlands	4 Participants n=4 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	1 Participants n=1 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	5 Participants n=5 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Argentina	5 Participants n=5 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	8 Participants n=8 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	13 Participants n=13 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Turkey	5 Participants n=5 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	7 Participants n=7 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	12 Participants n=12 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Belgium	7 Participants n=7 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	6 Participants n=6 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	13 Participants n=13 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment United States	9 Participants n=9 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	11 Participants n=11 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	20 Participants n=20 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Brazil	13 Participants n=13 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	21 Participants n=21 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	34 Participants n=34 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Italy	9 Participants n=9 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	8 Participants n=8 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	17 Participants n=17 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Israel	6 Participants n=6 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	2 Participants n=2 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	8 Participants n=8 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment France	3 Participants n=3 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	2 Participants n=2 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	5 Participants n=5 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Germany	17 Participants n=17 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	8 Participants n=8 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	25 Participants n=25 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Region of Enrollment Spain	6 Participants n=6 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	6 Participants n=6 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	12 Participants n=12 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
Age, Continuous	59.5 years STANDARD_DEVIATION 9.87 • n=87 Participants	59.3 years STANDARD_DEVIATION 9.96 • n=85 Participants	59.4 years STANDARD_DEVIATION 9.89 • n=172 Participants
Sex: Female, Male Female	33 Participants n=87 Participants	32 Participants n=85 Participants	65 Participants n=172 Participants
Sex: Female, Male Male	54 Participants n=87 Participants	53 Participants n=85 Participants	107 Participants n=172 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=87 Participants	24 Participants n=85 Participants	37 Participants n=172 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=87 Participants	33 Participants n=85 Participants	78 Participants n=172 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	29 Participants n=87 Participants	28 Participants n=85 Participants	57 Participants n=172 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=87 Participants	1 Participants n=85 Participants	1 Participants n=172 Participants
Race (NIH/OMB) Asian	1 Participants n=87 Participants	0 Participants n=85 Participants	1 Participants n=172 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=87 Participants	0 Participants n=85 Participants	0 Participants n=172 Participants
Race (NIH/OMB) Black or African American	1 Participants n=87 Participants	2 Participants n=85 Participants	3 Participants n=172 Participants
Race (NIH/OMB) White	81 Participants n=87 Participants	80 Participants n=85 Participants	161 Participants n=172 Participants
Race (NIH/OMB) More than one race	0 Participants n=87 Participants	0 Participants n=85 Participants	0 Participants n=172 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=87 Participants	2 Participants n=85 Participants	6 Participants n=172 Participants
Region of Enrollment Canada	1 Participants n=1 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	1 Participants n=1 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.	2 Participants n=2 Participants • All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.

PRIMARY outcome

Timeframe: Randomization Date to Disease Progression or Death From Any Cause Up to 18.3 Months

Population: All randomized participants. Participants censored in Cixutumumab arm = 20 and Pemetrexed + Cisplatin arm = 21.

PFS was defined as the time from date of randomization until the date of disease progression, or death from any cause, whichever was first. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation for disease progression or death were censored at the date of last tumor assessment. The PFS was estimated following the Kaplan-Meier method.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Progression-free Survival (PFS)	5.45 months Interval 3.88 to 6.05	5.22 months Interval 4.24 to 6.74

SECONDARY outcome

Timeframe: Randomization to Disease Progression Up to 18.3 Months

Population: All randomized participants

The ORR is the percentage of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1. Disease progression was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. ORR is confirmed best overall tumor response of CR and PR. CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Percentage of Participants Achieving an Objective Response Rate (ORR)	37.9 percentage of participants Interval 27.7 to 49.0	30.6 percentage of participants Interval 21.0 to 41.5

SECONDARY outcome

Timeframe: Randomization Date to Death From Any Cause Up to 20 Months

Population: All randomized participants. Participants censored cixutumumab arm = 47 and pemetrexed + cisplatin arm = 39.

Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive. OS was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Overall Survival (OS)	10.68 Months Interval 8.74 to The upper limit was not estimable due to the data had insufficient overall survival data events.	10.38 Months Interval 7.43 to 14.39

SECONDARY outcome

Timeframe: Time from Response to Disease Progression or Death from Any Cause Up to 20 Months

Population: All randomized participants who had CR or PR. Participants censored in Cixutumumab arm = 10 and Pemetrexed + Cisplatin arm = 8.

Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for PD is met, or death, is objectively documented. DOR was estimated using the Kaplan-Meier method. Disease progression was assessed via RECIST version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing non-target lesions

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=33 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=26 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Duration of Response (DOR)	4.90 Months Interval 4.17 to 6.28	3.91 Months Interval 2.92 to 6.41

SECONDARY outcome

Timeframe: Randomization Date to Disease Progression Up to 18.3 Months

Population: All randomized participants. Participants censored in Cixutumumab arm = 39 and in the Pemetrexed + Cisplatin arm = 36.

TTPS was defined as the time from the date of randomization until the date of disease progression. Disease progression was assessed via RECIST version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing non-target lesions.TTPS was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Time to Progressive Disease (TTPS)	6.05 Months Interval 5.32 to 7.79	6.05 Months Interval 4.93 to 7.89

SECONDARY outcome

Timeframe: Time to worsening of symptoms as measured by LCSS score Up to 18.3 Months

Population: All randomized participants. Participants censored in Cixutumumab arm = 38 and Pemetrexed + Cisplatin arm = 46.

TTPS was defined as the time from the date of randomization until the date of worsening of symptoms as measured by Lung Cancer Symptom Scale (LCSS) score. Symptomatic progression was defined as an increase (worsening) of the Average Symptomatic Burden Index (ASBI) that is, the mean of the six major lung cancer specific symptom scores of the LCSS patient scale - ranging from 0 to 100 where higher score indicates worst outcome). For each participant, the maximum improvement over baseline score was calculated for each of the 9 LCSS items, ASBI and LCSS total score. Participants without event are censored at the date of the last LCSS assessment. TTPS was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Time to Worsening of Symptoms as Measured by Lung Cancer Symptom Scale (LCSS) Score	2.14 Months Interval 1.54 to 2.99	4.21 Months Interval 2.43 to 5.36

SECONDARY outcome

Timeframe: Change from baseline measurement to the end of Cycle 2, average of 42 days

Population: All randomized participants.

CTS was measured by percentage change of tumor size at the end of Cycle 2 comparing to baseline tumor size.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=87 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=85 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Change in Tumor Size (CTS)	-23.88 Percent Change Standard Deviation 18.859	-16.04 Percent Change Standard Deviation 26.143

SECONDARY outcome

Timeframe: First Infusion: [Prior to Infusion (of Cycle1): 1, 72, 168, 336 hours(hrs) and 504 hrs (i.e. Prior to Infusion of Cycle 2)] and Fourth Infusion; [Prior to Infusion (of Cycle 4),1,24,72,120,168,240,336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 5)]

Population: Participants who were randomized to the cixutumumab arm and had evaluable PK data.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=71 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Cixutumumab, Cycle 1 (First Infusion) and Cycle 4 (Fourth Infusion) First Infusion	481 microgram/milliliter (ug/mL) Geometric Coefficient of Variation 33	—
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Cixutumumab, Cycle 1 (First Infusion) and Cycle 4 (Fourth Infusion) Fourth Infusion	556 microgram/milliliter (ug/mL) Geometric Coefficient of Variation 17	—

SECONDARY outcome

Timeframe: Prior to Infusion (of Cycle 1), 1, 72, 168, 336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 2)

Population: Participants who were randomized to the cixutumumab arm and had evaluable PK data.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=57 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
PK: Area Under the Concentration Time Curve (AUC[0-inf]) of Cixutumumab, Cycle 1 (i.e. First Infusion)	73200 microgram*hour/milliliter (ug*hr/mL) Geometric Coefficient of Variation 35	—

SECONDARY outcome

Timeframe: Prior to Infusion (of Cycle 4), 1, 24, 72, 120, 168, 240, 336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 5)

Population: Participants who were randomized to the cixutumumab arm and had evaluable PK data.

Outcome measures

Measure	Pemetrexed + Cisplatin + Cixutumumab n=27 Participants Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
PK: Area Under the Concentration Time Curve During 1 Dosing Interval (i.e. 504 hr, AUC(0-tau) of Cixutumumab, Cycle 4 (i.e. Fourth Infusion)	79700 (ug*hr/mL) Geometric Coefficient of Variation 30	—

SECONDARY outcome

Timeframe: Preinfusion, Cycle 2, Cycle 4, Cycle 8, Postinfusion, 30-Day Follow-Up

Population: Zero participants were analyzed for PD Biomarker IGF-I, total IGF-I, and IGFBP-3 due to blood samples were not collected in order to assess biomarker data.

Blood samples for the determination of PD marker concentrations were collected at the specified time points for all participants. Analysis of the following markers include free IGF-I, total IGF-I, and IGFBP-3.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Preinfusion, Cycle1(C1): 1, 72, 168, 240, 336 hours(hrs); C2 and C3: 1, 168, 336 hrs; C4: 1, 24,72,120,168, 240, 336, 504 hrs, Postinfusion; 30 Day Follow Up

Population: Zero participants were analyzed due to no immunogenicity analysis was done and the assay was never developed.

Outcome measures

Outcome data not reported

Adverse Events

Pemetrexed + Cisplatin + Cixutumumab

Serious events: 49 serious events

Other events: 83 other events

Deaths: 0 deaths

Pemetrexed + Cisplatin

Serious events: 31 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pemetrexed + Cisplatin + Cixutumumab n=85 participants at risk Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=81 participants at risk Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Blood and lymphatic system disorders Anaemia	7.1% 6/85 • Number of events 18 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Febrile neutropenia	3.5% 3/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Leukopenia	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Neutropenia	4.7% 4/85 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Pancytopenia	2.4% 2/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Thrombocytopenia	1.2% 1/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Cardiac disorders Atrial fibrillation	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Cardiac disorders Myocardial infarction	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Cardiac disorders Pericarditis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Ear and labyrinth disorders Vertigo	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Ear and labyrinth disorders Vestibular disorder	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Eye disorders Blindness	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Abdominal pain	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Colitis	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Constipation	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Diarrhoea	3.5% 3/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Inguinal hernia	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Nausea	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Oesophagitis	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Stomatitis	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Vomiting	8.2% 7/85 • Number of events 9 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Fatigue	8.2% 7/85 • Number of events 9 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders General physical health deterioration	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Malaise	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Mucosal inflammation	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Non-cardiac chest pain	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Pyrexia	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Sudden death	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Hepatobiliary disorders Cholecystitis	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Immune system disorders Hypersensitivity	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Dengue fever	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Device related infection	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Empyema	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Lobar pneumonia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Lung abscess	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Lung infection	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	3.7% 3/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Mucosal infection	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Pneumonia	3.5% 3/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Pneumonia klebsiella	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Pneumonia pneumococcal	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Postoperative abscess	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Sepsis	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Septic shock	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Streptococcal bacteraemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Blood bilirubin increased	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Blood creatinine increased	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Neutrophil count decreased	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Platelet count decreased	3.5% 3/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations White blood cell count decreased	2.4% 2/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Decreased appetite	4.7% 4/85 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Dehydration	4.7% 4/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyperkalaemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyperuricaemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hypoalbuminaemia	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hypocalcaemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyponatraemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Compartment syndrome	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Cerebral ischaemia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Ischaemic stroke	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Nervous system disorder	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Peripheral motor neuropathy	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Peripheral sensory neuropathy	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Seizure	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Spinal cord compression	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Syncope	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Transient ischaemic attack	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Psychiatric disorders Confusional state	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Renal and urinary disorders Acute kidney injury	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Renal and urinary disorders Renal failure	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	3.7% 3/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.5% 3/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Surgical and medical procedures Osteosynthesis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Embolism	0.00% 0/85 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Extremity necrosis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Haematoma	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Hypertension	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Hypotension	2.4% 2/85 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Peripheral arterial occlusive disease	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Peripheral artery thrombosis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Venous thrombosis	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.

Other adverse events

Measure	Pemetrexed + Cisplatin + Cixutumumab n=85 participants at risk Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.	Pemetrexed + Cisplatin n=81 participants at risk Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Blood and lymphatic system disorders Anaemia	38.8% 33/85 • Number of events 103 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	44.4% 36/81 • Number of events 98 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Leukopenia	7.1% 6/85 • Number of events 12 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 27 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Neutropenia	14.1% 12/85 • Number of events 29 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	21.0% 17/81 • Number of events 35 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Blood and lymphatic system disorders Thrombocytopenia	9.4% 8/85 • Number of events 31 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 9 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Ear and labyrinth disorders Vertigo	10.6% 9/85 • Number of events 11 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Eye disorders Lacrimation increased	9.4% 8/85 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	8.6% 7/81 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Abdominal pain	4.7% 4/85 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	13.6% 11/81 • Number of events 15 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Constipation	31.8% 27/85 • Number of events 39 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	23.5% 19/81 • Number of events 28 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Diarrhoea	22.4% 19/85 • Number of events 29 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	19.8% 16/81 • Number of events 21 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Dyspepsia	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	3.7% 3/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Dysphagia	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Nausea	52.9% 45/85 • Number of events 74 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	50.6% 41/81 • Number of events 101 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Stomatitis	16.5% 14/85 • Number of events 24 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Gastrointestinal disorders Vomiting	34.1% 29/85 • Number of events 41 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	34.6% 28/81 • Number of events 55 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Asthenia	11.8% 10/85 • Number of events 12 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	11.1% 9/81 • Number of events 30 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Chest pain	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Fatigue	42.4% 36/85 • Number of events 82 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	40.7% 33/81 • Number of events 63 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Influenza like illness	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Mucosal inflammation	14.1% 12/85 • Number of events 18 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	3.7% 3/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Non-cardiac chest pain	3.5% 3/85 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Oedema peripheral	8.2% 7/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	16.0% 13/81 • Number of events 19 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
General disorders Pyrexia	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	12.3% 10/81 • Number of events 14 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Conjunctivitis	3.5% 3/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Infections and infestations Upper respiratory tract infection	2.4% 2/85 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Alanine aminotransferase increased	9.4% 8/85 • Number of events 11 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Aspartate aminotransferase increased	4.7% 4/85 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Blood creatinine increased	14.1% 12/85 • Number of events 18 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	19.8% 16/81 • Number of events 20 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Neutrophil count decreased	10.6% 9/85 • Number of events 24 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Platelet count decreased	7.1% 6/85 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	11.1% 9/81 • Number of events 14 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations Weight decreased	20.0% 17/85 • Number of events 28 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	13.6% 11/81 • Number of events 13 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Investigations White blood cell count decreased	5.9% 5/85 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Decreased appetite	28.2% 24/85 • Number of events 36 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	33.3% 27/81 • Number of events 32 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Dehydration	11.8% 10/85 • Number of events 13 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyperglycaemia	50.6% 43/85 • Number of events 156 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	19.8% 16/81 • Number of events 45 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyperkalaemia	5.9% 5/85 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hypocalcaemia	5.9% 5/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hypokalaemia	7.1% 6/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hypomagnesaemia	10.6% 9/85 • Number of events 13 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	7.4% 6/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Metabolism and nutrition disorders Hyponatraemia	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Back pain	10.6% 9/85 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	12.3% 10/81 • Number of events 13 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Bone pain	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 5/85 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	2.5% 2/81 • Number of events 2 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Dizziness	12.9% 11/85 • Number of events 13 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Dysgeusia	8.2% 7/85 • Number of events 9 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	9.9% 8/81 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Nervous system disorders Paraesthesia	2.4% 2/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Psychiatric disorders Anxiety	3.5% 3/85 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 6 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Psychiatric disorders Depression	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 4 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Psychiatric disorders Insomnia	5.9% 5/85 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	8.6% 7/81 • Number of events 10 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Cough	15.3% 13/85 • Number of events 21 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	19.8% 16/81 • Number of events 20 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.5% 14/85 • Number of events 21 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	19.8% 16/81 • Number of events 26 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.2% 7/85 • Number of events 11 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	0.00% 0/81 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Respiratory, thoracic and mediastinal disorders Productive cough	1.2% 1/85 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	6.2% 5/81 • Number of events 14 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Skin and subcutaneous tissue disorders Alopecia	8.2% 7/85 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	3.7% 3/81 • Number of events 3 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Skin and subcutaneous tissue disorders Rash	8.2% 7/85 • Number of events 7 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	4.9% 4/81 • Number of events 5 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
Vascular disorders Hypotension	9.4% 8/85 • Number of events 8 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.	1.2% 1/81 • Number of events 1 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60