A Study in Non-Small Cell Lung Cancer | NCT01232452

ID	Type	Description	Link
I5A-MC-JAEM	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Pemetrexed + Cisplatin + Cixutumumab	Experimental	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 patients 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.	Drug: Pemetrexed Drug: Cisplatin Drug: Cixutumumab
Pemetrexed + Cisplatin	Active Comparator	Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 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 patients 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.	Drug: Pemetrexed Drug: Cisplatin

Name	Type	Description	Arm Group Labels	Other Names
Pemetrexed	Drug	Administered intravenously (IV)	Pemetrexed + Cisplatin Pemetrexed + Cisplatin + Cixutumumab

Measure	Description	Time Frame
Progression-free Survival (PFS)	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.	Randomization Date to Disease Progression or Death From Any Cause Up to 18.3 Months

Measure	Description	Time Frame
Percentage of Participants Achieving an Objective Response Rate (ORR)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participant has histologically or cytologically confirmed, nonsquamous (adenocarcinoma/large cell or other) NSCLC.
The participant has Stage IV disease at the time of study entry.
Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 14 days prior to randomization, or after surgical resection performed at least 28 days prior to randomization. The participant may have no evidence of Grade 1 (or greater) Central Nervous System (CNS) hemorrhage based on pretreatment scans(performed within 21 days before randomization).
The participant has measurable or nonmeasurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 guidelines.
The participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
If prior adjuvant or neoadjuvant chemotherapy, the last dose of adjuvant or neoadjuvant treatment was administered at least 6 months prior to randomization.
The participant has adequate bone marrow reserve, and renal and hepatic function
The participant has fasting serum glucose less than or equal to 125 mg/dL, and hemoglobin A1C less than or equal to 6%.
Females with reproductive potential: Must have a negative serum or urine pregnancy test within 7 days prior to the first dose of any study drug.
Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 6 months following the last dose of any study drug.
The participant has the ability to understand and the willingness to sign a written informed consent form.
Previous radiation therapy is allowed to less than 25% of the bone marrow, but should have been limited and must not have included whole pelvis radiation.
The participant has archived tumor tissue available for analysis (can be either primary tumor or metastases).
The participant has an estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Participants who have squamous histology.
The participant's tumor fully or partially contains Small Cell Lung Cancer (SCLC).
The participant has leptomeningeal disease.
The participant is currently or has previously received chemotherapy for advanced (Stage IV) NSCLC.
The participant has a history of treatment with other agents targeting the Insulin-like or Epidermal Growth factor receptors.
Participants who have received prior Pemetrexed treatment.
The patient has a known allergy/history of hypersensitivity reaction to any of the treatment components.
The participant has diabetes mellitus as defined by being treated with glucose lowering medications in the past 3 months prior to enrollment.
The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia,or psychiatric/social situations that would limit compliance with study requirements.
The participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy.
The participant has undergone major surgery within 28 days prior to randomization.
The participant has received a prior autologous or allogeneic organ or tissue transplantation.
The participant is pregnant or lactating.
The participant has a history of another primary cancer, with the exception of the following: curatively resected nonmelanomatous skin cancer, curatively treated carcinoma in situ, or other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 5 years.
The participant has superior vena cava syndrome contraindicating hydration.
The participant has current clinically-relevant coronary artery disease (New York Heart Association III or IV) or uncontrolled congestive heart failure.
The participant has any Grade 2 (or greater) peripheral neuropathy.
The participant has clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
The participant is unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
The participant is unwilling or unable to take premedications (folic acid, vitamin B12, or corticosteroids) required by the pemetrexed label.
The participant has received a recent (within 30 days of enrollment) or is receiving concurrent yellow fever vaccination.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Chicago	Illinois	60611

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS)

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.

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

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	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.

Units	Counts
Participants	OG00087 OG00185

Title

Denominators

Categories

Title	Measurements
	OG0005.45(3.88 to 6.05) OG0015.22(4.24 to 6.74)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.848		Hazard Ratio (HR)	1.03			2-Sided	95	0.73	1.47					Superiority

Secondary

Percentage of Participants Achieving an Objective Response Rate (ORR)

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.

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

Randomization to Disease Progression Up to 18.3 Months

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	Pemetrexed + Cisplatin

Secondary

Overall Survival (OS)

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.

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

Posted

Median

95% Confidence Interval

Months

Randomization Date to Death From Any Cause Up to 20 Months

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	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.

Secondary

Duration of Response (DOR)

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

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	Pemetrexed + Cisplatin

Secondary

Time to Progressive Disease (TTPS)

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.

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

Posted

Median

95% Confidence Interval

Months

Randomization Date to Disease Progression Up to 18.3 Months

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	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.

Secondary

Time to Worsening of Symptoms as Measured by Lung Cancer Symptom Scale (LCSS) Score

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.

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001

Secondary

Change in Tumor Size (CTS)

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

All randomized participants.

Posted

Mean

Standard Deviation

Percent Change

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	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.

Secondary

Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Cixutumumab, Cycle 1 (First Infusion) and Cycle 4 (Fourth Infusion)

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

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram/milliliter (ug/mL)

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)]

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.

Units	Counts
Participants	OG000

Secondary

PK: Area Under the Concentration Time Curve (AUC[0-inf]) of Cixutumumab, Cycle 1 (i.e. First Infusion)

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

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram*hour/milliliter (ug*hr/mL)

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.

Units	Counts
Participants	OG000

Secondary

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)

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

Posted

Geometric Mean

Geometric Coefficient of Variation

(ug*hr/mL)

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)

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.

Units	Counts
Participants	OG000

Secondary

Pharmacodynamics (PD) Markers: Free Insulin-like Growth Factor-I (IGF-I, Total IGF-I, and IGF Binding Proteins (IGFBP-3)

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.

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.

Posted

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.
OG001	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.

Secondary

Immunogenicity of Cixutumumab

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

Posted

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

ID	Title	Description
OG000	Pemetrexed + Cisplatin + Cixutumumab	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.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00018 events6 affected85 at risk EG0011 events1 affected81 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected85 at risk EG0015 events5 affected81 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected85 at risk EG0013 events2 affected81 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0007 events2 affected85 at risk EG0010 events0 affected81 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0003 events1 affected85 at risk EG0014 events1 affected81 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Pericarditis	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG0010 events0 affected81 at risk
Vestibular disorder	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Blindness	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Colitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected85 at risk EG0010 events0 affected81 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0010 events0 affected81 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0011 events1 affected81 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0011 events1 affected81 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0010 events0 affected81 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0009 events7 affected85 at risk EG0011 events1 affected81 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG0009 events7 affected85 at risk EG0011 events1 affected81 at risk
General physical health deterioration	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Malaise	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Mucosal inflammation	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0010 events0 affected81 at risk
Pyrexia	General disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0012 events2 affected81 at risk
Sudden death	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0010 events0 affected81 at risk
Hypersensitivity	Immune system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Dengue fever	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Device related infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Empyema	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Lobar pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Lung abscess	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Lung infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0014 events3 affected81 at risk
Mucosal infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected85 at risk EG0011 events1 affected81 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Postoperative abscess	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Sepsis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0011 events1 affected81 at risk
Septic shock	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0017 events4 affected81 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Blood bilirubin increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG0010 events0 affected81 at risk
Blood creatinine increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Neutrophil count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Platelet count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0007 events3 affected85 at risk EG0010 events0 affected81 at risk
White blood cell count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0007 events2 affected85 at risk EG0010 events0 affected81 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected85 at risk EG0010 events0 affected81 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0005 events4 affected85 at risk EG0010 events0 affected81 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0010 events0 affected81 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0013 events1 affected81 at risk
Nervous system disorder	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0010 events0 affected81 at risk
Seizure	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Spinal cord compression	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Syncope	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Confusional state	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0010 events0 affected81 at risk
Renal failure	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0010 events0 affected81 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0012 events2 affected81 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG0013 events3 affected81 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected85 at risk EG0012 events2 affected81 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected85 at risk EG0013 events2 affected81 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0012 events1 affected81 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0011 events1 affected81 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Osteosynthesis	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Embolism	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected85 at risk EG0011 events1 affected81 at risk
Extremity necrosis	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Haematoma	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Hypertension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0010 events0 affected81 at risk
Hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0004 events2 affected85 at risk EG0010 events0 affected81 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Peripheral artery thrombosis	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk
Venous thrombosis	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0010 events0 affected81 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG000103 events33 affected85 at risk EG00198 events36 affected81 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00012 events6 affected85 at risk EG00127 events5 affected81 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00029 events12 affected85 at risk EG00135 events17 affected81 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00031 events8 affected85 at risk EG0019 events5 affected81 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG00011 events9 affected85 at risk EG0014 events4 affected81 at risk
Lacrimation increased	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0008 events8 affected85 at risk EG00110 events7 affected81 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0006 events4 affected85 at risk EG00115 events11 affected81 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00039 events27 affected85 at risk EG00128 events19 affected81 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00029 events19 affected85 at risk EG00121 events16 affected81 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0014 events3 affected81 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0011 events1 affected81 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00074 events45 affected85 at risk EG001101 events41 affected81 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00024 events14 affected85 at risk EG0018 events6 affected81 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00041 events29 affected85 at risk EG00155 events28 affected81 at risk
Asthenia	General disorders	MedDRA 14.1	Systematic Assessment	EG00012 events10 affected85 at risk EG00130 events9 affected81 at risk
Chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG00110 events5 affected81 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG00082 events36 affected85 at risk EG00163 events33 affected81 at risk
Influenza like illness	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG0017 events6 affected81 at risk
Mucosal inflammation	General disorders	MedDRA 14.1	Systematic Assessment	EG00018 events12 affected85 at risk EG0013 events3 affected81 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0004 events3 affected85 at risk EG0016 events6 affected81 at risk
Oedema peripheral	General disorders	MedDRA 14.1	Systematic Assessment	EG0007 events7 affected85 at risk EG00119 events13 affected81 at risk
Pyrexia	General disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG00114 events10 affected81 at risk
Conjunctivitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0005 events3 affected85 at risk EG0016 events5 affected81 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected85 at risk EG0017 events6 affected81 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.1	Systematic Assessment	EG00011 events8 affected85 at risk EG0016 events4 affected81 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected85 at risk EG0017 events5 affected81 at risk
Blood creatinine increased	Investigations	MedDRA 14.1	Systematic Assessment	EG00018 events12 affected85 at risk EG00120 events16 affected81 at risk
Neutrophil count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00024 events9 affected85 at risk EG00110 events6 affected81 at risk
Platelet count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0006 events6 affected85 at risk EG00114 events9 affected81 at risk
Weight decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00028 events17 affected85 at risk EG00113 events11 affected81 at risk
White blood cell count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00010 events5 affected85 at risk EG0016 events4 affected81 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG00036 events24 affected85 at risk EG00132 events27 affected81 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG00013 events10 affected85 at risk EG0018 events6 affected81 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG000156 events43 affected85 at risk EG00145 events16 affected81 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0008 events5 affected85 at risk EG0013 events2 affected81 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0007 events5 affected85 at risk EG0011 events1 affected81 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0007 events6 affected85 at risk EG0014 events4 affected81 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG00013 events9 affected85 at risk EG0016 events6 affected81 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0015 events4 affected81 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG00010 events9 affected85 at risk EG00113 events10 affected81 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG0015 events5 affected81 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0006 events5 affected85 at risk EG0012 events2 affected81 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00013 events11 affected85 at risk EG0017 events5 affected81 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0009 events7 affected85 at risk EG00110 events8 affected81 at risk
Paraesthesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected85 at risk EG0015 events5 affected81 at risk
Anxiety	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected85 at risk EG0016 events5 affected81 at risk
Depression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG0014 events4 affected81 at risk
Insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected85 at risk EG00110 events7 affected81 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG00021 events13 affected85 at risk EG00120 events16 affected81 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG00021 events14 affected85 at risk EG00126 events16 affected81 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG00011 events7 affected85 at risk EG0010 events0 affected81 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected85 at risk EG00114 events5 affected81 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0008 events7 affected85 at risk EG0013 events3 affected81 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0007 events7 affected85 at risk EG0015 events4 affected81 at risk
Hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0008 events8 affected85 at risk EG0011 events1 affected81 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D008175	Lung Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

ID	Title	Description
BG000	Pemetrexed + Cisplatin + Cixutumumab	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pemetrexed + Cisplatin + Cixutumumab	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.			49	85	83	85
EG001	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.			31	81	79	81