A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01287520
• Collaborator: (none)
• Enrollment: 41
• Locations: 2
• Arm: 1
• Duration (Months): 41
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine a recommended Phase 2 dose and dosing regimen of LY2090314 in combination with pemetrexed and carboplatin in patients with advanced/metastatic cancer. Part A of this study will consist of dose escalation of the study regimen, and Part B will consist of an expanded cohort to confirm the dose provided from Part A.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer	Drug: LY2090314; Drug: pemetrexed; Drug: Carboplatin; Other: ranitidine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: LY2090314/pemetrexed/carboplatin Part A, Cycle 1 (28 days): Intravenous doses of LY2090314 starting at 10 milligram (mg) were given on Day 1 followed by 10 mg LY2090314, 500 milligram per square meter (mg/m^2) pemetrexed (intravenous dose), and 5 or 6 area under the concentration-time curve (AUC) intravenous dose of carboplatin on Day 8. Part A, Cycle 2 (21 days): Pemetrexed and carboplatin given on Day 1 at the same dose administered in Cycle 1. Part A, Cycle 3 (21 days) and beyond: LY2090314, Pemetrexed and carboplatin were given on Day 1 at the same dose administered in Cycle 1. LY2090314 doses were escalated until the maximum tolerated dose (MTD) was reached. Part B: Dose determined in Part A was administered. Participants were allowed to continue the combination treatment if they were receiving therapeutic benefit until they fulfilled one of the criteria for discontinuation.

Drug: LY2090314; Administered intravenously; Drug: pemetrexed; Administered intravenously; Other Names: Alimta LY231514 ; Drug: Carboplatin; Administered intravenously; Other: ranitidine; Per I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine given as pretreatment to LY2090314 for stomach pain.

Outcome Measures

Primary Outcome Measures

1. Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD]) [Baseline up to Day 28 (Cycle 1)]

   Recommended Phase 2 MTD was determined, when a dose limiting toxicity (DLT) occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a DLT occurred in 2 or more participants, accrual to the cohort was stopped, as the MTD was exceeded. A DLT was defined as an adverse event (AE) occurring in Cycle 1 (28 days) that was possibly related to study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0, ≥Grade 3 nonhematologic toxicity (except for nausea/vomiting without maximal symptomatic/prophylactic treatment) possibly or likely related to the study medication;CTCAE Grade 4 hematological toxicity of >5 days duration; Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; CTCAE ≥Grade 2 thrombocytopenia plus bleeding; CTCAE ≥Grade 3 prolonged QTc interval.

Secondary Outcome Measures

1. Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314 [Cycle 1 Day 1 of a 28 day cycle]

   AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone.

2. PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb) [Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle]

   AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb.

3. PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 [Cycle 1 Day 1 of a 28-day cycle]

4. PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb) [Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle]

5. Number of Participants With Best Overall Tumor Response [Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)]

   Best overall observed tumor response at any point during the study until disease progression/recurrence defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria.

6. Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem) [Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle]

   AUC0-∞ was calculated from the area under the concentration versus time curves of Pem given as a single dose with Carb (doublet therapy) and when co-administered with Carb and LY2090314 (triplet therapy).

7. PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem) [Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle]

   Cmax of Pem given as a single dose with Carb (doublet therapy) and when coadministered with Carb and LY2090314 (triplet therapy).

8. PK Parameter: AUC0-∞ of Free Carboplatin (Carb) [Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle]

   AUC0-∞ of free Carb was calculated from the area under the concentration versus time curves of Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

9. PK Parameter: Cmax of Free Carboplatin [Cycle 1, Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle]

   Cmax of free Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

10. Pharmacodynamic (PD) Changes in Beta-Catenin (β-catenin) [Baseline, Cycle 1 , Day 1 of a 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycles]

    PD change from baseline to endpoint (up to Cycle 9) in β-catenin levels in peripheral blood mononuclear cells (PBMCs) following the administration of LY2090314 given alone and in combination with Pem and Carb. This outcome measure was not analyzed due to insufficient data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have a life expectancy of greater than or equal to 12 weeks

• Males and females with reproductive potential agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug

• Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease for which no proven effective therapy exists

• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)

• Have adequate hematologic, hepatic, and renal function

• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy.

Exclusion Criteria:

• Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication

• Have serious preexisting medical conditions (left to discretion of investigator)

• Have one of the following conduction abnormalities: Corrected time between start of Q wave and end of T wave (QTc) prolongation >450 millisecond (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long-QT-syndrome, or left bundle branch block (LBBB)

• Are taking any concomitant medication that may cause QTc prolongation, or induce Torsades de Pointes

• Have systolic blood pressure greater than or equal to 140 millimeters of Mercury (mm Hg), and diastolic blood pressure greater than or equal to 90 mm Hg that is not controlled by medical therapy

• Have serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher; have history of arrhythmia that is symptomatic or requires treatment

• Have chronic atrial fibrillation and/or bradycardia

• Have uncorrected electrolyte disorders including potassium <3.4 molar equivalent per liter (mEq/L) (<3.4 millimole per liter [mmol/l]), calcium <8.4 milligram per deciliter (mg/dL) (2.1 mmol/L), or magnesium <1.2 mg/dL (<0.62 mmol/L)

• Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required)

• Have a hematologic malignancy

• Females who are pregnant or lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Tampa	Florida	United States
2	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.	Nashville	Tennessee	United States

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01287520
• Other Study ID Numbers: 11613; I2H-MC-JWYA
• First Posted: Feb 1, 2011
• Last Update Posted: Feb 25, 2019
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Neoplasm Metastasis; Carboplatin; Pemetrexed; Ranitidine; Ranitidine bismuth citrate

Study Results

Participant Flow

Pre-assignment Detail	The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have "completed" the trial if they discontinued treatment due to progressive disease or an adverse event.

Arm/Group Title	LY 10/Carb 5/Pem 500 (Cohort 1)	LY 10/Carb 6/Pem 500 (Cohort 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohort 4)	LY 80/Carb 6/Pem 500 (Cohort 5)	LY 120/Carb 6/Pem 500 -(Cohort 6)	LY 80/Carb 6/Pem 500 + R50 (Cohort 7)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)	LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 milligrams (mg) LY2090314 (LY) administered by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 milligrams per meter squared (mg/m^2) pemetrexed (Pem) administered by intravenous infusion followed by Area Under the Time Curve (AUC) 5 milligrams per milliliter times minutes (mg/mL * min) carboplatin (Carb) administered by intravenous infusion. Cycle 2 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem administered by intravenous infusion followed by AUC 5 mg/mL * min Carb administered by intravenous infusion followed by 10 mg LY2090314 administered by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 and beyond: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28 -ay cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up and beyond: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine (R50) intravenous, 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem IV infusion. Cycle 3 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by IV infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 and beyond: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine IV pretreatment and 40 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Period Title: Overall Study
STARTED	3	7	5	7	3	4	2	5	5
COMPLETED	0	0	0	0	0	0	0	0	0
NOT COMPLETED	3	7	5	7	3	4	2	5	5

Baseline Characteristics

Arm/Group Title	LY 10/Carb 5/Pem 500 (Cohort 1)	LY 10/Carb 6/Pem 500 (Cohort 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohort 4)	LY 80/Carb 6/Pem 500 (Cohort 5)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 80/Carb 6/Pem 500 + R50 (Cohort 7)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)	LY 40/Carb 6/Pem 500 + R50 (Cohort 9)	Total
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Total of all reporting groups
Overall Participants	3	7	5	7	3	4	2	5	5	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.81 (11.88)	55.27 (9.19)	59.31 (5.62)	58.32 (8.95)	57.35 (7.59)	56.73 (7.52)	55.39 (9.86)	58.78 (9.06)	61.35 (4.41)	57.79 (7.65)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	3 42.9%	5 100%	3 42.9%	2 66.7%	0 0%	0 0%	3 60%	0 0%	18 43.9%
Male	1 33.3%	4 57.1%	0 0%	4 57.1%	1 33.3%	4 100%	2 100%	2 40%	5 100%	23 56.1%
Race/Ethnicity, Customized (participants) [Number]
African	0 0%	0 0%	1 20%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	2 4.9%
Caucasian	3 100%	6 85.7%	4 80%	7 100%	2 66.7%	4 100%	2 100%	5 100%	5 100%	38 92.7%
Hispanic	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Region of Enrollment (participants) [Number]
United States	3 100%	7 100%	5 100%	7 100%	3 100%	4 100%	2 100%	5 100%	5 100%	41 100%
Body Surface Area (meters squared (m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters squared (m^2)]	1.76 (0.11)	2.10 (0.13)	1.66 (0.14)	1.94 (0.29)	1.77 (0.46)	2.11 (0.33)	2.07 (0.14)	1.90 (0.30)	2.04 (0.15)	1.94 (0.27)
Eastern Cooperative Oncology Group (ECOG) performance (participants) [Number]
0	3 100%	5 71.4%	5 100%	7 100%	2 66.7%	4 100%	2 100%	3 60%	5 100%	36 87.8%
1	0 0%	2 28.6%	0 0%	0 0%	1 33.3%	0 0%	0 0%	2 40%	0 0%	5 12.2%
Basis of Diagnosis (participants) [Number]
Cytological	1 33.3%	1 14.3%	1 20%	1 14.3%	2 66.7%	0 0%	1 50%	1 20%	0 0%	8 19.5%
Histopathological	2 66.7%	6 85.7%	4 80%	6 85.7%	1 33.3%	4 100%	1 50%	4 80%	5 100%	33 80.5%
Initial Pathological Tumor Diagnosis (participants) [Number]
Mesothelioma	2 66.7%	3 42.9%	1 20%	0 0%	0 0%	1 25%	0 0%	1 20%	1 20%	9 22%
Non-small cell lung carcinoma (NSCLC)	0 0%	0 0%	3 60%	1 14.3%	1 33.3%	0 0%	0 0%	1 20%	1 20%	7 17.1%
Leimyosarcoma	0 0%	2 28.6%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	3 7.3%
Esophagus	0 0%	0 0%	0 0%	1 14.3%	1 33.3%	0 0%	0 0%	1 20%	0 0%	3 7.3%
Lung adenocarcinoma	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	1 20%	1 20%	3 7.3%
Rectum	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	2 4.9%
Small cell lung carcinoma (SCLC)	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	1 20%	2 4.9%
Gastric	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 20%	2 4.9%
Head and neck	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Adenocarcinoma not otherwise specified (NOS)	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Colon	0 0%	0 0%	1 20%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Breast	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Pancreas	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Cancer NOS	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Gall bladder	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Thymoma	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	1 2.4%
Adenoid	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	0 0%	0 0%	1 2.4%
Bile duct	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 20%	0 0%	1 2.4%

Outcome Measures

1. Primary Outcome

Title	Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD])
Description	Recommended Phase 2 MTD was determined, when a dose limiting toxicity (DLT) occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a DLT occurred in 2 or more participants, accrual to the cohort was stopped, as the MTD was exceeded. A DLT was defined as an adverse event (AE) occurring in Cycle 1 (28 days) that was possibly related to study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0, ≥Grade 3 nonhematologic toxicity (except for nausea/vomiting without maximal symptomatic/prophylactic treatment) possibly or likely related to the study medication;CTCAE Grade 4 hematological toxicity of >5 days duration; Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; CTCAE ≥Grade 2 thrombocytopenia plus bleeding; CTCAE ≥Grade 3 prolonged QTc interval.
Time Frame	Baseline up to Day 28 (Cycle 1)

Outcome Measure Data

Analysis Population Description

Safety population: all participants who have received at least 1 dose of the study drug.

Arm/Group Title	LY2090314/Pemetrexed/Carboplatin
Arm/Group Description	Cycle 1 (28 days) Cohorts 1 to 3 Cycle 1 Day 1: 10-20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 or 6 mg/mL * min Carb by intravenous infusion. Cohorts 4 to 9, Cohorts 7 to 9 were pretreated with 50 mg ranitidine intravenous-Cycle 1 Day 1: 40-120 mg LY2090314 by intravenous infusion. -Cycle 1 Day 8: 500 mg/m^2 by Pem intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40-120 mg LY2090314 by intravenous infusion.
Measure Participants	41
Number [milligrams (mg)]	40

2. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314
Description	AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone.
Time Frame	Cycle 1 Day 1 of a 28 day cycle

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of LY2090314 and had evaluable AUC0-∞ data, excluding 2 participants (1 in dose groups LY80 and 1 in dose group LY120) who received the wrong dose of LY2090314.

Arm/Group Title	LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)	LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion-followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 49 mg LY2090314 by intravenous infusion. Cohort 9, LY2090314 pretreated with 50 mg ranitidine intravenous. Based on I2H-MV-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cohort 7, LY2090314 pretreated with 50 mg ranitidine intravenous. Based on I2H-MV-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 by Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by pretreatment with 50 mg ranitidine intravenous and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	10	5	11	5	3	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter]	216 (26.3)	427 (21.8)	976 (42.6)	1870 (76.7)	3310 (18.7)	1600 (47.3)

3. Secondary Outcome

Title	PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
Description	AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb.
Time Frame	Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose LY2090314 coadministered with Pem and Carb and had enough samples to allow estimation of AUC0-∞ parameters excluding 2 participants (1 in dose groups LY80 and 1 in dose group LY120) who received the incorrect dose of LY2090314.

Arm/Group Title	LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)	LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cohort 9, LY2090314 pretreated with 50 mg ranitidine intravenous. Based on I2H-MC-JWYa Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cohort 7, LY2090314 pretreated with 50 mg ranitidine intravenous. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 by Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by pretreatment with 50 mg ranitidine intravenous and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	10	4	9	3	1	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter]	192 (48.2)	404 (33.2)	938 (33.5)	1830 (7.84)	2190 (NA)	1570 (36.5)

4. Secondary Outcome

Title	PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314
Time Frame	Cycle 1 Day 1 of a 28-day cycle

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of LY2090314 and had evaluable AUC0-∞ data, excluding 2 participants (1 in dose groups LY80 and 1 in dose group LY120) who received the incorrect dose of LY2090314.

Arm/Group Title	LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohorts 4 and 9 )	LY 80/Carb 6/Pem 500 (Cohorts 5 and 7	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by LY2090314 20 mg by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 49 mg LY2090314 by intravenous infusion. Cohort 9, LY2090314 pretreated with 50 mg ranitidine IV. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cohort 7, LY2090314 pretreated with 50 mg ranitidine IV. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 by Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by IV infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by pretreatment with 50 mg ranitidine intravenous and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	10	5	11	5	3	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	122 (21.5)	246 (29.0)	603 (47.7)	898 (50.5)	1700 (63.2)	881 (53.3)

5. Secondary Outcome

Title	PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
Time Frame	Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of LY2090314 and had evaluable AUC0-∞ data, excluding 2 participants (1 in dose groups LY80 and 1 in dose group LY120) who received the incorrect dose of LY2090314.

Arm/Group Title	LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)	LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 (Cohort 1) or AUC 6 (Cohort 2) mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cohort 9, LY2090314 pretreated with 50 mg ranitidine intravenous. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cohort 7, LY2090314 pretreated with 50 mg ranitidine IV. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 by Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by pretreatment with 50 mg ranitidine intravenous and 60 mg LY2090314 intravenous infusion. Based on I2H-MC_JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	10	4	9	3	1	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	106 (57.5)	271 (62.5)	657 (44.1)	1150 (27.8)	768 (NA)	1040 (48.2)

6. Secondary Outcome

Title	Number of Participants With Best Overall Tumor Response
Description	Best overall observed tumor response at any point during the study until disease progression/recurrence defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria.
Time Frame	Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)

Outcome Measure Data

Analysis Population Description

Analysis population: all participants who received at least 1 dose of study drug and had tumor response assessment.

Arm/Group Title	LY 10/Carb 5/Pem 500 (Cohort 1)	LY 10/Carb 6/Pem 500 (Cohort 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohort 4)	LY 80/Carb 6/Pem 500 (Cohort 5)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 80/Carb 6/Pem 500 + R50 (Cohort 7)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)	LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 IV infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 intravenous Pem infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min by Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	3	7	5	7	3	4	2	5	5
CR	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
PR	0 0%	0 0%	1 20%	1 14.3%	0 0%	0 0%	1 50%	1 20%	0 0%
SD	2 66.7%	4 57.1%	2 40%	2 28.6%	0 0%	0 0%	1 50%	1 20%	2 40%
PD	0 0%	2 28.6%	1 20%	3 42.9%	1 33.3%	0 0%	0 0%	2 40%	2 40%
Unknown (discontinued before response assessment)	1 33.3%	1 14.3%	1 20%	0 0%	2 66.7%	0 0%	0 0%	0 0%	1 20%

7. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem)
Description	AUC0-∞ was calculated from the area under the concentration versus time curves of Pem given as a single dose with Carb (doublet therapy) and when co-administered with Carb and LY2090314 (triplet therapy).
Time Frame	Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who were treated with Pem and Carb (doublet therapy) or who were treated with Pem, Carb and LY2090314 (triplet therapy) and had evaluable AUC0-∞ Pem data.

Arm/Group Title	Pemetrexed (Doublet Therapy)	Pemetrexed (Triplet Therapy)
Arm/Group Description	Pem with Carb Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem and AUC 5 or AUC 6 mg/mL * min Carb on Cycle 1, Day 8 of 28-day cycle by intravenous infusion. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion on Cycle 2 Day 1 of 21-day cycle	Pem with Carb and LY2090314 Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 or AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg up to 20 mg LY2090314 by intravenous infusion on Cycle 2 up to Cycle 10: Day 1 of 21-day cycle. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg up to 120 mg of LY2090314 by intravenous infusion on Cycle 1, Day 8 of 28-day cycle and Cycle 3 up to Cycle 10: Day 1 of 21-day cycle. Based on I2H-MC-JWYA Protocol Amendment (D) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain to participants in Cohorts 7, 8 and 9.
Measure Participants	33	36
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter/ milligram]	212 (34.4)	202 (37.5)

8. Secondary Outcome

Title	PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem)
Description	Cmax of Pem given as a single dose with Carb (doublet therapy) and when coadministered with Carb and LY2090314 (triplet therapy).
Time Frame	Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who were treated with Pem and Carb (doublet therapy) or who were treated with Pem, Carb and LY2090314 (triplet therapy) and had evaluable Cmax Pem data.

Arm/Group Title	Pemetrexed (Doublet Therapy)	Pemetrexed (Triplet Therapy)
Arm/Group Description	Pem with Carb Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem and AUC 5 or AUC 6 mg/mL * min Carb on Cycle 1, Day 8 of 28-day cycle by intravenous infusion. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion on Cycle 2 Day 1 of 21-day cycle	Pem with Carb and LY2090317 Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 or AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg up to 20 mg LY2090314 by intravenous infusion on Cycle 2 up to Cycle 10: Day 1 of 21-day cycle. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg up to 120 mg of LY2090314 by intravenous infusion on Cycle 1, Day 8 of 28-day cycle and Cycle 3 up to Cycle 10: Day 1 of 21-day cycle. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain to participants in Cohorts 7, 8 and 9.
Measure Participants	33	36
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter per milligram]	109 (38.0)	108 (43.1)

9. Secondary Outcome

Title	PK Parameter: AUC0-∞ of Free Carboplatin (Carb)
Description	AUC0-∞ of free Carb was calculated from the area under the concentration versus time curves of Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).
Time Frame	Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who were treated with Pem and Carb (doublet therapy) or Pem, Carb and LY2090314 (triplet therapy) and who had evaluable Carb AUC0-∞ data.

Arm/Group Title	Carboplatin (Doublet Therapy)	Carboplatin (Triplet Therapy)
Arm/Group Description	Carb and Pem Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem and AUC 5 or AUC 6 mg/mL * min Carb on Cycle 1, Day 8 of 28-day cycle by intravenous infusion. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion on Cycle 2 Day 1 of 21-day cycle	Carb with Pem and LY2090314 Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 or AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg up to 20 mg LY2090314 by intravenous infusion on Cycle 2 up to Cycle 9: Day 1 of 21-day cycle. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg up to 120 mg of LY2090314 by intravenous infusion on Cycle 1, Day 8 of 28-day cycle and Cycle 3 up to Cycle 9: Day 1 of 21-day cycle. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain to participants in Cohorts 7, 8 and 9.
Measure Participants	32	35
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms per milliliter per mg]	81.6 (41.8)	88.1 (49.2)

10. Secondary Outcome

Title	PK Parameter: Cmax of Free Carboplatin
Description	Cmax of free Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).
Time Frame	Cycle 1, Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

Outcome Measure Data

Analysis Population Description

All participants who were treated with Pem and Carb (doublet therapy) or who were treated with Pem, Carb and LY2090314 (triplet therapy) and had evaluable Carb Cmax data.

Arm/Group Title	Carboplatin (Doublet Therapy)	Carboplatin (Triplet Therapy)
Arm/Group Description	Carb and Pem Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem and AUC 5 or AUC 6 mg/mL * min Carb on Cycle 1, Day 8 of 28-day cycle by intravenous infusion. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion on Cycle 2 Day 1 of 21-day cycle	Carb and Pem with LY2090314 Participants in Cohorts 1, 2 and 3 were administered 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 or AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg up to 20 mg LY2090314 by intravenous infusion on Cycle 2 up to Cycle 9: Day 1 of 21-day cycle. Participants in Cohorts 4 through 9 were administered 500 mg/m^2 Pem and AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg up to 120 mg of LY2090314 by intravenous infusion on Cycle 1, Day 8 of 28-day cycle and Cycle 3 up to Cycle 10: Day 1 of 21-day cycle. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain to participants in Cohorts 7, 8 and 9.
Measure Participants	32	35
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter/milligram]	24.0 (43.9)	25.5 (46.0)

11. Secondary Outcome

Title	Pharmacodynamic (PD) Changes in Beta-Catenin (β-catenin)
Description	PD change from baseline to endpoint (up to Cycle 9) in β-catenin levels in peripheral blood mononuclear cells (PBMCs) following the administration of LY2090314 given alone and in combination with Pem and Carb. This outcome measure was not analyzed due to insufficient data.
Time Frame	Baseline, Cycle 1 , Day 1 of a 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycles

Outcome Measure Data

Analysis Population Description

There was insufficient data from participants who received at least 1 dose of LY2090314 to perform β-catenin modeling, thus zero participants were analyzed.

Arm/Group Title	LY 10/Carb 5/Pem 500 (Cohort 1)	LY 10/Carb 6/Pem 500 (Cohort 2)	LY 20/Carb 6/Pem 500 (Cohort 3)	LY 40/Carb 6/Pem 500 (Cohort 4)	LY 80/Carb 6/Pem 500 (Cohort 5)	LY 120/Carb 6/Pem 500 (Cohort 6)	LY 80/Carb 6/Pem 500 + R50 (Cohort 7)	LY 60/Carb 6/Pem 500 + R50 (Cohort 8)	LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
Arm/Group Description	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by IV infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 5 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 10 mg LY2090314 by IV infusion. Cycle 1 Day 8 of 28-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 -ay cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: 120 mg LY2090314 mg by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 10: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine IV pretreatment and 60 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.	Cycle 1 Day 1 of 28-day cycle: pretreated with 50 mg ranitidine intravenous, 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28-day cycle 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21-day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21-day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 intravenous infusion. Based on I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
Measure Participants	0	0	0	0	0	0	0	0	0

Adverse Events

Arm/Group Title	LY 10/Carb 5/Pem 500 (Cohort 1)		LY 10/Carb 6/Pem 500 (Cohort 2)		LY 20/Carb 6/Pem 500 (Cohort 3)		LY 40/Carb 6/Pem 500 (Cohort 4)		LY 80/Carb 6/Pem 500 (Cohort 5)		LY 120/Carb 6/Pem 500 (Cohort 6)		LY 80/Carb 6/Pem 500 + R50 (Cohort 7)		LY 60/Carb 6/Pem 500 + R50 (Cohort 8)		LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
Arm/Group Description	Cycle 1 Day 1 of 28 day cycle: 10 mg LY2090314 administered by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem administered by intravenous infusion followed by AUC 5 mg/mL * min Carb administered by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem administered by intravenous infusion followed by AUC 5 mg/mL * min Carb administered by intravenous infusion followed by 10 mg LY2090314 administered by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: 10 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 by Pem intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: 20 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion. Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: 120 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem by intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 120 mg LY2090314 by intravenous infusion.		Cycle 1 Day 1 of 28 day cycle: pretreated with 50 mg ranitidine intravenous, 80 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 80 mg LY2090314 intravenous infusion. Based on I2H-MV-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.		Cycle 1 Day 1 of 28 day cycle: pretreated with 50 mg ranitidine intravenous, 60 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 60 mg LY2090314 intravenous infusion. Based on I2H-MV-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.		Cycle 1 Day 1 of 28 day cycle: pretreated with 50 mg ranitidine intravenous, 40 mg LY2090314 by intravenous infusion. Cycle 1 Day 8 of 28 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6mg/mL * min Carb intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40mmg LY2090314 40 mg by intravenous infusion. Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL * min Carb by intravenous infusion followed by 500 mg/m^2 Pem intravenous infusion. Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m^2 Pem by intravenous infusion followed by AUC 6 mg/mL * min Carb by intravenous infusion followed by 50 mg ranitidine intravenous pretreatment and 40 mg LY2090314 intravenous infusion. Based on I2H-MV-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine was given as a pretreatment to LY2090314 as prophylaxis for stomach pain.
All Cause Mortality
	LY 10/Carb 5/Pem 500 (Cohort 1)		LY 10/Carb 6/Pem 500 (Cohort 2)		LY 20/Carb 6/Pem 500 (Cohort 3)		LY 40/Carb 6/Pem 500 (Cohort 4)		LY 80/Carb 6/Pem 500 (Cohort 5)		LY 120/Carb 6/Pem 500 (Cohort 6)		LY 80/Carb 6/Pem 500 + R50 (Cohort 7)		LY 60/Carb 6/Pem 500 + R50 (Cohort 8)		LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY 10/Carb 5/Pem 500 (Cohort 1)		LY 10/Carb 6/Pem 500 (Cohort 2)		LY 20/Carb 6/Pem 500 (Cohort 3)		LY 40/Carb 6/Pem 500 (Cohort 4)		LY 80/Carb 6/Pem 500 (Cohort 5)		LY 120/Carb 6/Pem 500 (Cohort 6)		LY 80/Carb 6/Pem 500 + R50 (Cohort 7)		LY 60/Carb 6/Pem 500 + R50 (Cohort 8)		LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		3/7 (42.9%)		3/5 (60%)		2/7 (28.6%)		1/3 (33.3%)		1/4 (25%)		1/2 (50%)		0/5 (0%)		1/5 (20%)
Cardiac disorders
Angina pectoris	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Nausea	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Rectal haemorrhage	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Vomiting	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
General disorders
Chest pain	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Pyrexia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Infections and infestations
Pneumonia	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Pseudomembranous colitis	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Musculoskeletal chest pain	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Panic attack	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Pleural effusion	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Vascular disorders
Deep vein thrombosis	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	LY 10/Carb 5/Pem 500 (Cohort 1)		LY 10/Carb 6/Pem 500 (Cohort 2)		LY 20/Carb 6/Pem 500 (Cohort 3)		LY 40/Carb 6/Pem 500 (Cohort 4)		LY 80/Carb 6/Pem 500 (Cohort 5)		LY 120/Carb 6/Pem 500 (Cohort 6)		LY 80/Carb 6/Pem 500 + R50 (Cohort 7)		LY 60/Carb 6/Pem 500 + R50 (Cohort 8)		LY 40/Carb 6/Pem 500 + R50 (Cohort 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		7/7 (100%)		5/5 (100%)		7/7 (100%)		3/3 (100%)		3/4 (75%)		2/2 (100%)		5/5 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)	3	6/7 (85.7%)	8	5/5 (100%)	5	5/7 (71.4%)	5	2/3 (66.7%)	3	0/4 (0%)	0	1/2 (50%)	1	4/5 (80%)	4	3/5 (60%)	5
Leukocytosis	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Leukopenia	0/3 (0%)	0	4/7 (57.1%)	4	1/5 (20%)	1	3/7 (42.9%)	8	2/3 (66.7%)	3	0/4 (0%)	0	1/2 (50%)	2	2/5 (40%)	2	1/5 (20%)	2
Lymphopenia	0/3 (0%)	0	4/7 (57.1%)	4	1/5 (20%)	1	3/7 (42.9%)	4	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Neutropenia	0/3 (0%)	0	4/7 (57.1%)	7	2/5 (40%)	6	5/7 (71.4%)	14	3/3 (100%)	4	0/4 (0%)	0	1/2 (50%)	1	3/5 (60%)	6	2/5 (40%)	4
Thrombocytopenia	2/3 (66.7%)	2	3/7 (42.9%)	8	2/5 (40%)	3	6/7 (85.7%)	17	2/3 (66.7%)	5	0/4 (0%)	0	2/2 (100%)	5	4/5 (80%)	8	3/5 (60%)	9
Cardiac disorders
Bundle branch block left	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Cardiac flutter	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Palpitations	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Eye disorders
Asthenopia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Cataract	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Eye irritation	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	0/5 (0%)	0
Lacrimation increased	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	0/5 (0%)	0
Vision blurred	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Visual impairment	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Vitreous floaters	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Abdominal distension	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Abdominal pain	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	3/7 (42.9%)	3	2/3 (66.7%)	3	2/4 (50%)	2	1/2 (50%)	1	2/5 (40%)	2	0/5 (0%)	0
Abdominal pain lower	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Abdominal pain upper	0/3 (0%)	0	2/7 (28.6%)	2	0/5 (0%)	0	2/7 (28.6%)	2	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	1/5 (20%)	2	1/5 (20%)	1
Ascites	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Constipation	2/3 (66.7%)	2	1/7 (14.3%)	1	2/5 (40%)	2	2/7 (28.6%)	2	2/3 (66.7%)	3	0/4 (0%)	0	2/2 (100%)	2	0/5 (0%)	0	2/5 (40%)	2
Diarrhoea	0/3 (0%)	0	1/7 (14.3%)	1	1/5 (20%)	1	2/7 (28.6%)	2	2/3 (66.7%)	2	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
Dyspepsia	0/3 (0%)	0	0/7 (0%)	0	2/5 (40%)	2	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	0/5 (0%)	0
Dysphagia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Flatulence	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
Haematochezia	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Haemorrhoids	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Nausea	1/3 (33.3%)	3	6/7 (85.7%)	8	3/5 (60%)	5	4/7 (57.1%)	5	1/3 (33.3%)	1	1/4 (25%)	1	2/2 (100%)	3	2/5 (40%)	3	3/5 (60%)	5
Retching	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Toothache	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Vomiting	1/3 (33.3%)	1	2/7 (28.6%)	2	2/5 (40%)	3	3/7 (42.9%)	4	3/3 (100%)	3	1/4 (25%)	1	2/2 (100%)	3	1/5 (20%)	1	0/5 (0%)	0
General disorders
Asthenia	0/3 (0%)	0	1/7 (14.3%)	1	1/5 (20%)	1	1/7 (14.3%)	1	1/3 (33.3%)	1	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Catheter site phlebitis	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Chest discomfort	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/4 (25%)	1	1/2 (50%)	1	0/5 (0%)	0	1/5 (20%)	1
Chest pain	0/3 (0%)	0	2/7 (28.6%)	2	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/4 (25%)	1	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Chills	0/3 (0%)	0	1/7 (14.3%)	1	2/5 (40%)	2	1/7 (14.3%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	1/5 (20%)	1
Fatigue	3/3 (100%)	3	6/7 (85.7%)	8	5/5 (100%)	6	5/7 (71.4%)	6	2/3 (66.7%)	2	0/4 (0%)	0	1/2 (50%)	1	4/5 (80%)	4	4/5 (80%)	4
Influenza like illness	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Infusion site reaction	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Mucosal inflammation	1/3 (33.3%)	1	0/7 (0%)	0	2/5 (40%)	2	2/7 (28.6%)	2	1/3 (33.3%)	2	0/4 (0%)	0	2/2 (100%)	2	0/5 (0%)	0	0/5 (0%)	0
Nodule	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Oedema peripheral	1/3 (33.3%)	1	1/7 (14.3%)	1	1/5 (20%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Pyrexia	0/3 (0%)	0	3/7 (42.9%)	4	3/5 (60%)	6	2/7 (28.6%)	2	1/3 (33.3%)	2	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	2/5 (40%)	3
Immune system disorders
Drug hypersensitivity	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Hypersensitivity	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Infections and infestations
Gastroenteritis	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Lung infection	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Nasopharyngitis	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Streptococcal bacteraemia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	2/7 (28.6%)	4	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Injury, poisoning and procedural complications
Incision site pain	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Infusion related reaction	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	2/5 (40%)	5	0/5 (0%)	0
Scratch	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Investigations
Alanine aminotransferase increased	0/3 (0%)	0	1/7 (14.3%)	1	2/5 (40%)	3	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Antineutrophil cytoplasmic antibody increased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Aspartate aminotransferase increased	0/3 (0%)	0	1/7 (14.3%)	1	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Blood alkaline phosphatase increased	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Blood creatinine increased	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Blood culture positive	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Blood glucose increased	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Blood magnesium decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	2	0/5 (0%)	0	0/5 (0%)	0
Blood urine present	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Electrocardiogram qt prolonged	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Glomerular filtration rate decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Haematocrit decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Haemoglobin decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Neutrophil count decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Weight decreased	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
White blood cell count decreased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	3/5 (60%)	4
White blood cell count increased	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)	0	3/7 (42.9%)	3	2/5 (40%)	2	4/7 (57.1%)	4	2/3 (66.7%)	3	1/4 (25%)	1	1/2 (50%)	1	3/5 (60%)	3	0/5 (0%)	0
Dehydration	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	2/7 (28.6%)	2	2/3 (66.7%)	4	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Hypercalcaemia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Hyperglycaemia	0/3 (0%)	0	4/7 (57.1%)	6	1/5 (20%)	1	3/7 (42.9%)	4	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	1/5 (20%)	1
Hyperkalaemia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Hyperphosphatasaemia	0/3 (0%)	0	2/7 (28.6%)	2	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Hypoalbuminaemia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Hypomagnesaemia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	1/7 (14.3%)	4	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Hyponatraemia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	3/7 (42.9%)	3	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Type 2 diabetes mellitus	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	2	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Back pain	2/3 (66.7%)	2	2/7 (28.6%)	3	0/5 (0%)	0	2/7 (28.6%)	2	0/3 (0%)	0	1/4 (25%)	1	0/2 (0%)	0	0/5 (0%)	0	2/5 (40%)	2
Bone pain	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Muscular weakness	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Musculoskeletal chest pain	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Myalgia	0/3 (0%)	0	1/7 (14.3%)	2	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Pain in extremity	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	1/5 (20%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Nervous system disorders
Burning sensation	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Dizziness	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	2/7 (28.6%)	2	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	2/5 (40%)	2
Dysgeusia	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Headache	0/3 (0%)	0	1/7 (14.3%)	1	2/5 (40%)	2	3/7 (42.9%)	3	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Hypogeusia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Neuropathy peripheral	3/3 (100%)	3	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Paraesthesia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Peripheral sensory neuropathy	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	1/5 (20%)	1
Somnolence	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Syncope	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Agitation	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Anxiety	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Confusional state	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	2/7 (28.6%)	2	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Insomnia	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Renal and urinary disorders
Dysuria	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Renal pain	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Urinary retention	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Reproductive system and breast disorders
Vaginal haemorrhage	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Vulvovaginal pruritus	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	3/7 (42.9%)	3	2/5 (40%)	2	3/7 (42.9%)	3	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Dyspnoea	0/3 (0%)	0	3/7 (42.9%)	4	2/5 (40%)	2	4/7 (57.1%)	7	1/3 (33.3%)	1	1/4 (25%)	1	0/2 (0%)	0	2/5 (40%)	2	2/5 (40%)	2
Dyspnoea exertional	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Epistaxis	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
Hiccups	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Hypoxia	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Nasal congestion	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Nasal mucosal discolouration	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Oropharyngeal pain	0/3 (0%)	0	2/7 (28.6%)	2	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Paranasal sinus hypersecretion	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Productive cough	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Pulmonary embolism	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Rhinalgia	0/3 (0%)	0	1/7 (14.3%)	1	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Rhinorrhoea	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Sinus congestion	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Wheezing	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)	0	2/7 (28.6%)	2	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Hyperhidrosis	0/3 (0%)	0	0/7 (0%)	0	1/5 (20%)	1	0/7 (0%)	0	1/3 (33.3%)	1	1/4 (25%)	1	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Hypoaesthesia facial	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	2	0/5 (0%)	0	0/5 (0%)	0
Night sweats	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
Pruritus	0/3 (0%)	0	0/7 (0%)	0	2/5 (40%)	2	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Rash	1/3 (33.3%)	2	4/7 (57.1%)	4	1/5 (20%)	1	2/7 (28.6%)	2	0/3 (0%)	0	0/4 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/5 (0%)	0
Rash erythematous	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	2	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Rash pruritic	1/3 (33.3%)	1	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Skin disorder	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Surgical and medical procedures
Frontal sinus operation	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Vascular disorders
Flushing	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Hypertension	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	1/4 (25%)	1	0/2 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Hypotension	0/3 (0%)	0	0/7 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.