A Study in Non Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01139775
• Recruitment Status: Completed
• First Posted: June 9, 2010
• Results First Posted: May 18, 2018
• Last Update Posted: May 18, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer
• Interventions: Drug: Pemetrexed; Drug: Cisplatin; Drug: LY2603618
• Enrollment: 76

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 milligrams per square meter (mg/m^2) + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 milligrams (mg) After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered intravenously (IV) over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes and cisplatin was administered IV over 1 hour.
Period Title: Overall Study
Started	14	39	23
Received at Least 1 Dose of Study Drug	14	39	22
Completed	13	26	17
Not Completed	1	13	6
Reason Not Completed
Adverse Event	0	6	2
Protocol Violation	0	5	0
Withdrawal by Subject	1	0	2
Physician Decision	0	2	2

Baseline Characteristics

Arm/Group Title		Phase 1: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin	Total
Arm/Group Description		Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.	Total of all reporting groups
Overall Number of Baseline Participants		14	39	23	76
Baseline Analysis Population Description		All participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	14 participants	39 participants	23 participants	76 participants
		57.9 (11.4)	57.9 (10.1)	56.4 (9.8)	57.4 (10.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	14 participants	39 participants	23 participants	76 participants
	Female	7	15	8	30
	Male	7	24	15	46
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
White	Number Analyzed	14 participants	39 participants	23 participants	76 participants
		14	39	23	76
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	14 participants	39 participants	23 participants	76 participants
Spain		7	24	12	43
Germany		7	15	11	33
Initial Pathological Diagnosis; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	14 participants	39 participants	23 participants	76 participants
Adenocarcinoma, Bronchiolalveolar		0	0	1	1
Adenocarcinoma, Colon		1	0	0	1
Adenocarcinoma, Lung		8	38	19	65
Adenocarcinoma, Moderately Diff., Lung		0	0	1	1
Carcinoma, Ampulla of Vater		1	0	0	1
Carcinoma, Breast		1	0	0	1
Carcinoma, Large Cell, Lung		0	0	1	1
Carcinoma, Lung		0	1	0	1
Carcinoma, Non-small Cell, Poorly Diff, Lung		1	0	0	1
Carcinoma, Pancreas		1	0	0	1
Mesothelioma, Malignum		1	0	0	1
Pleuritis Carcinomatosa		0	0	1	1
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	14 participants	39 participants	23 participants	76 participants
ECOG Status 0		11	9	7	27
ECOG Status 1		3	30	15	48
Missing		0	0	1	1
		[1] Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death) as follows: 0 - Fully Active; 1 - Ambulatory, Restricted Strenuous Activity; 2 - Ambulatory, No Work Activities; 3 - Partially Confined to Bed, Limited Self Care; 4 - Completely Disabled; and 5 - Dead.

Outcome Measures

1. Primary Outcome

Title	Phase 2: Progression-Free Survival Time
Description	Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.
Time Frame	Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment)

Outcome Measure Data

Analysis Population Description

All randomized Phase 2 participants.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	39	23
Median (90% Confidence Interval); Unit of Measure: months
	4.7; (4.2 to 7.1)	1.5; (1.3 to 2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Pemetrexed + Cisplatin + LY2603618, Phase 2: Pemetrexed + Cisplatin
	Comments	The analysis for comparing progression-free survival time between the treatment arms used a Bayesian Augmented Control model with a hierarchical random-effects distribution on treatment effects. The final model incorporated historical data from a completed Phase 3 study (NCT00789373) to augment the prospective control arm data.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Bayesian Posterior Probability
	Estimated Value	0.96
	Estimation Comments	Pemetrexed + cisplatin + LY2603618 was considered superior to pemetrexed + cisplatin if the posterior probability of superiority exceeded 0.85.

2. Primary Outcome

Title	Phase 1: Recommended Phase 2 Dose of LY2603618
Description	The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-∞)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]).
Time Frame	Time of first dose to last dose

Outcome Measure Data

Analysis Population Description

Phase 1 participants who received at least 1 dose of any of the study drugs.

Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed	14
Measure Type: Number; Unit of Measure: mg
	275

3. Secondary Outcome

Title	Phase 2: Overall Survival
Description	Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.
Time Frame	Randomization to the date of death from any cause through the time of study discontinuation (approximately 12 months after last participant was randomized)

Outcome Measure Data

Analysis Population Description

All randomized Phase 2 participants.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	39	23
Median (90% Confidence Interval); Unit of Measure: months
	12.9 [1]; (9.3 to NA)	6.6; (4.2 to 19.4)

[1]

The upper bound of the 90% confidence interval was not calculable.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Pemetrexed + Cisplatin + LY2603618, Phase 2: Pemetrexed + Cisplatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2294
	Comments	The test of treatment effect was conducted at a 2-sided alpha level of 0.10.
	Method	Log Rank
	Comments	[Not Specified]

4. Secondary Outcome

Title	Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR)
Description	Overall response rate is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time Frame	Randomization until date of disease progression (up to 6 months after the last participant was randomized)

Outcome Measure Data

Analysis Population Description

All randomized Phase 2 participants.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	39	23
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
	43.6; (28.0 to 60.0)	21.7; (7.0 to 44.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Pemetrexed + Cisplatin + LY2603618, Phase 2: Pemetrexed + Cisplatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0824
	Comments	The test of treatment effect was conducted at a 2-sided alpha level of 0.10.
	Method	Chi-squared
	Comments	[Not Specified]

5. Secondary Outcome

Title	Phase 2: Change in Tumor Size
Description	Change in tumor size was based on tumor measurements collected according to RECIST, v1.1 guidelines. Tumor size is the sum of the tumor measurements (longest diameters) of target lesions at each tumor evaluation. Change in tumor size was defined as the change in log tumor size from baseline evaluation to the evaluation at the end of Cycle 2.
Time Frame	Baseline, end of Cycle 2

Outcome Measure Data

Analysis Population Description

Participants with measureable disease (target lesions) at baseline who received at least 1 dose of study drug.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	39	22
Mean (Standard Deviation); Unit of Measure: centimeters
	-0.30 (0.541)	-0.14 (0.277)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Pemetrexed + Cisplatin + LY2603618, Phase 2: Pemetrexed + Cisplatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4924
	Comments	The test of treatment effect was conducted at a 2-sided alpha level of 0.10.
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

6. Secondary Outcome

Title	Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
Description	Cmax is reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.
Time Frame	Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose

Outcome Measure Data

Analysis Population Description

Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.

Arm/Group Title		Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:		Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed		13
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
130 mg, Cycle 1/Day 2	Number Analyzed	3 participants
		1810; (14%)
130 mg, Cycle 2/Day 2	Number Analyzed	3 participants
		1730; (43%)
185 mg, Cycle 1/Day 2	Number Analyzed	3 participants
		2200; (33%)
185 mg, Cycle 2/Day 2	Number Analyzed	3 participants
		2190; (58%)
240 mg, Cycle 1/Day 2	Number Analyzed	3 participants
		3470; (27%)
240 mg, Cycle 2/Day 2	Number Analyzed	3 participants
		2750; (63%)
275 mg, Cycle 1/Day 2	Number Analyzed	3 participants
		4130; (29%)
275 mg, Cycle 2/Day 2	Number Analyzed	4 participants
		3620; (23%)

7. Secondary Outcome

Title	Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin)
Description	Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.
Time Frame	Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose.

Outcome Measure Data

Analysis Population Description

Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis.

Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed	14
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Pemetrexed	88300; (28%)
T-platinum from cisplatin	3710; (43%)

8. Secondary Outcome

Title	Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
Description	AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-∞]) values are reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.
Time Frame	Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose

Outcome Measure Data

Analysis Population Description

Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.

Arm/Group Title		Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:		Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed		13
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
130 mg, Cycle 1/Day 2, AUC(0-24)	Number Analyzed	3 participants
		8700; (30%)
130 mg, Cycle 2/Day 2, AUC(0-24)	Number Analyzed	3 participants
		9780; (43%)
130 mg, Cycle 1/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		10200; (26%)
130 mg, Cycle 2/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		11300; (44%)
130 mg, Cycle 1/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		10200; (26%)
130 mg, Cycle 2/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		11300; (45%)
185 mg, Cycle 1/Day 2, AUC(0-24)	Number Analyzed	3 participants
		13800; (119%)
185 mg, Cycle 2/Day 2, AUC(0-24)	Number Analyzed	3 participants
		12500; (170%)
185 mg, Cycle 1/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		18300; (192%)
185 mg, Cycle 2/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		14800; (217%)
185 mg, Cycle 1/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		18400; (193%)
185 mg, Cycle 2/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		15700; (253%)
240 mg, Cycle 1/Day 2, AUC(0-24)	Number Analyzed	3 participants
		26200; (19%)
240 mg, Cycle 2/Day 2, AUC(0-24)	Number Analyzed	3 participants
		22100; (31%)
240 mg, Cycle 1/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		32200; (21%)
240 mg, Cycle 2/Day 2, AUC(0-tlast)	Number Analyzed	3 participants
		27300; (31%)
240 mg, Cycle 1/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		32300; (21%)
240 mg, Cycle 2/Day 2, AUC(0-∞)	Number Analyzed	3 participants
		27500; (31%)
275 mg, Cycle 1/Day 2, AUC(0-24)	Number Analyzed	4 participants
		28900; (24%)
275 mg, Cycle 2/Day 2, AUC(0-24)	Number Analyzed	4 participants
		23500; (31%)
275 mg, Cycle 1/Day 2, AUC(0-tlast)	Number Analyzed	4 participants
		38100; (36%)
275 mg, Cycle 2/Day 2, AUC(0-tlast)	Number Analyzed	4 participants
		30800; (44%)
275 mg, Cycle 1/Day 2, AUC(0-∞)	Number Analyzed	4 participants
		38300; (37%)
275 mg, Cycle 2/Day 2, AUC(0-∞)	Number Analyzed	4 participants
		30900; (44%)

9. Secondary Outcome

Title	Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)
Description	AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.
Time Frame	Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose.

Outcome Measure Data

Analysis Population Description

Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis.

Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed	14
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
Pemetrexed, AUC(0-tlast)	159000; (35%)
Pemetrexed, AUC (0-∞)	160000; (35%)
T-platinum from cisplatin, AUC (0-tlast)	163000; (26%)
T-platinum from cisplatin, AUC (0-∞)	269000; (26%)

10. Secondary Outcome

Title	Phase 2: Pharmacokinetic: Cmax (LY2603618)
Description	[Not Specified]
Time Frame	Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose

Outcome Measure Data

Analysis Population Description

Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed	33
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	4130; (66%)

11. Secondary Outcome

Title	Phase 2: Pharmacokinetic: AUC (LY2603618)
Description	AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented.
Time Frame	Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose

Outcome Measure Data

Analysis Population Description

Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.

Arm/Group Title		Phase 2: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:		Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed		33
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
AUC (0-24)	Number Analyzed	32 participants
		31400; (49%)
AUC (0-tlast)	Number Analyzed	32 participants
		39300; (58%)
AUC (0-∞)	Number Analyzed	31 participants
		41100; (59%)

12. Secondary Outcome

Title	Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS)
Description	Health-related quality of life and participant symptoms were assessed using the LCSS (patient scale). However, improper implementation of questionnaires at the site level reduced the sponsor's ability to accurately evaluate the impacted data. Therefore, the LCSS data should be interpreted with caution. The LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. The total LCSS score was calculated as the mean of 9 questions from the LCSS.
Time Frame	Randomization to the end of study (approximately 12 months after the last participant entered treatment)

Outcome Measure Data

Analysis Population Description

All enrolled Phase 2 participants who had the baseline LCSS assessment and at least 1 post-baseline assessment.

Arm/Group Title		Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:		Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed		36	22
Mean (Standard Deviation); Unit of Measure: units on a scale
Total LCSS	Number Analyzed	32 participants	21 participants
		-10.7 (14.1)	-11.7 (15.1)
ASBI	Number Analyzed	34 participants	21 participants
		-11.6 (13.9)	-12.6 (15.4)

13. Secondary Outcome

Title	Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers
Description	Overall response rate is presented. Overall response rate is defined as the percentage of participants with a best response of CR or PR as classified by the investigators according to RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time Frame	Baseline through end of Phase 1

Outcome Measure Data

Analysis Population Description

All randomized Phase 1 participants.

Arm/Group Title		Phase 1: Pemetrexed + Cisplatin + LY2603618
Arm/Group Description:		Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
Overall Number of Participants Analyzed		14
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
130 mg	Number Analyzed	3 participants
		0; (0 to 0)
185 mg	Number Analyzed	3 participants
		66.7; (9.0 to 99.0)
240 mg	Number Analyzed	4 participants
		25.0; (1.0 to 81.0)
275 mg	Number Analyzed	4 participants
		0; (0 to 0)

14. Secondary Outcome

Title	Phase 2: Proportion of Participants Receiving Maintenance Therapy
Description	[Not Specified]
Time Frame	Cycle 5

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Treatment with LY2603618 was discontinued after 25 October 2012, data was not collected for analysis of the Phase 2: Proportion of Participants Receiving Maintenance Therapy.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

15. Secondary Outcome

Title	Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR)
Description	Clinical benefit rate is the best response CR, PR, or SD as classified by the investigators according to the RECIST, v1.1 guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time Frame	Randomization until date of disease progression or death (up to 6 months after the last participant was randomized)

Outcome Measure Data

Analysis Population Description

All randomized Phase 2 participants.

Arm/Group Title	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	39	23
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
	69.2; (52.0 to 83.0)	47.8; (27.0 to 69.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Pemetrexed + Cisplatin + LY2603618, Phase 2: Pemetrexed + Cisplatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0946
	Comments	The test of treatment effect was conducted at a 2-sided alpha level of 0.10.
	Method	Chi-squared
	Comments	[Not Specified]

16. Other Pre-specified Outcome

Title	Deaths
Description	Deaths that occurred during the study are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Randomization through 12 months after the last participant was randomized

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin + LY2603618	Phase 2: Pemetrexed + Cisplatin
Arm/Group Description:	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.	Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
Overall Number of Participants Analyzed	14	39	23
Measure Type: Count of Participants; Unit of Measure: Participants
Total deaths	0	21	15
Deaths while on treatment	0	3	1
Death within 30 days of last dose of study drug	0	1	0
Deaths during follow-up period	0	17	14

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Phase 1: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin
Arm/Group Description	Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.		Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.		Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
All-Cause Mortality
	Phase 1: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Phase 1: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.14%)		16/39 (41.03%)		6/22 (27.27%)
Blood and lymphatic system disorders
Anaemia † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Neutropenia † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Cardiac disorders
Angina pectoris † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Atrial fibrillation † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Gastrointestinal disorders
Ileus † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Nausea † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	1/22 (4.55%)	1
Vomiting † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
General disorders
Death † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Pyrexia † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Infections and infestations
Infection † 1	0/14 (0.00%)	0	1/39 (2.56%)	2	1/22 (4.55%)	1
Pneumonia † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Urinary tract infection bacterial † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Injury, poisoning and procedural complications
Femur fracture † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Tibia fracture † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Investigations
Blood creatinine increased † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Blood urea increased † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Metabolism and nutrition disorders
Hyperglycaemia † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Hypokalaemia † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Ketoacidosis † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Spinal pain † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Metastatic pain † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Nervous system disorders
Cerebrovascular accident † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Convulsion † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Ischaemic stroke † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Syncope † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Psychiatric disorders
Confusional state † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	1/22 (4.55%)	1
Pulmonary embolism † 1	1/14 (7.14%)	1	5/39 (12.82%)	5	0/22 (0.00%)	0
Respiratory failure † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	0/22 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Phase 1: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin + LY2603618		Phase 2: Pemetrexed + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100.00%)		37/39 (94.87%)		22/22 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	3/14 (21.43%)	16	7/39 (17.95%)	16	3/22 (13.64%)	6
Leukocytosis † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	2/22 (9.09%)	2
Leukopenia † 1	1/14 (7.14%)	2	5/39 (12.82%)	11	0/22 (0.00%)	0
Lymphopenia † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Neutropenia † 1	6/14 (42.86%)	13	8/39 (20.51%)	11	4/22 (18.18%)	7
Thrombocytopenia † 1	2/14 (14.29%)	10	1/39 (2.56%)	1	1/22 (4.55%)	1
Thrombocytosis † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Ear and labyrinth disorders
Ototoxicity † 1	0/14 (0.00%)	0	8/39 (20.51%)	22	1/22 (4.55%)	2
Tinnitus † 1	2/14 (14.29%)	4	5/39 (12.82%)	7	2/22 (9.09%)	2
Vertigo † 1	3/14 (21.43%)	4	2/39 (5.13%)	3	1/22 (4.55%)	1
Eye disorders
Conjunctivitis † 1	1/14 (7.14%)	9	2/39 (5.13%)	3	3/22 (13.64%)	4
Eye oedema † 1	0/14 (0.00%)	0	3/39 (7.69%)	4	1/22 (4.55%)	1
Eyelid oedema † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Lacrimation increased † 1	1/14 (7.14%)	1	2/39 (5.13%)	2	1/22 (4.55%)	1
Papilloedema † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	2/22 (9.09%)	2
Abdominal pain upper † 1	3/14 (21.43%)	3	1/39 (2.56%)	1	2/22 (9.09%)	2
Constipation † 1	2/14 (14.29%)	4	18/39 (46.15%)	30	8/22 (36.36%)	13
Diarrhoea † 1	3/14 (21.43%)	5	11/39 (28.21%)	17	4/22 (18.18%)	6
Dry mouth † 1	2/14 (14.29%)	2	1/39 (2.56%)	1	0/22 (0.00%)	0
Dyspepsia † 1	2/14 (14.29%)	2	2/39 (5.13%)	2	0/22 (0.00%)	0
Dysphagia † 1	1/14 (7.14%)	1	1/39 (2.56%)	1	1/22 (4.55%)	1
Flatulence † 1	2/14 (14.29%)	2	0/39 (0.00%)	0	0/22 (0.00%)	0
Gastritis † 1	1/14 (7.14%)	1	1/39 (2.56%)	1	0/22 (0.00%)	0
Gastrooesophageal reflux disease † 1	2/14 (14.29%)	2	1/39 (2.56%)	1	1/22 (4.55%)	1
Nausea † 1	12/14 (85.71%)	44	30/39 (76.92%)	106	15/22 (68.18%)	27
Toothache † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Vomiting † 1	7/14 (50.00%)	13	18/39 (46.15%)	42	6/22 (27.27%)	9
General disorders
Asthenia † 1	2/14 (14.29%)	2	17/39 (43.59%)	82	5/22 (22.73%)	12
Catheter site pain † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Catheter site related reaction † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Catheter site swelling † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Chest discomfort † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	1/22 (4.55%)	2
Chest pain † 1	0/14 (0.00%)	0	4/39 (10.26%)	4	2/22 (9.09%)	3
Chills † 1	1/14 (7.14%)	2	1/39 (2.56%)	2	3/22 (13.64%)	4
Fatigue † 1	13/14 (92.86%)	35	14/39 (35.90%)	23	14/22 (63.64%)	21
Infusion site extravasation † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Infusion site pain † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Mucosal inflammation † 1	2/14 (14.29%)	2	10/39 (25.64%)	22	4/22 (18.18%)	7
Oedema † 1	3/14 (21.43%)	3	4/39 (10.26%)	7	1/22 (4.55%)	1
Oedema peripheral † 1	3/14 (21.43%)	3	6/39 (15.38%)	10	3/22 (13.64%)	3
Pyrexia † 1	6/14 (42.86%)	8	10/39 (25.64%)	19	9/22 (40.91%)	10
Immune system disorders
Hypersensitivity † 1	1/14 (7.14%)	3	3/39 (7.69%)	3	0/22 (0.00%)	0
Infections and infestations
Bronchitis † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	2/22 (9.09%)	2
Candida infection † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Eye infection † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Gingivitis † 1	1/14 (7.14%)	2	0/39 (0.00%)	0	1/22 (4.55%)	1
Herpes simplex † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Laryngitis † 1	1/14 (7.14%)	1	1/39 (2.56%)	2	0/22 (0.00%)	0
Nasopharyngitis † 1	1/14 (7.14%)	1	5/39 (12.82%)	5	2/22 (9.09%)	2
Paronychia † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Pneumonia † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Respiratory tract infection † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	1/22 (4.55%)	1
Rhinitis † 1	2/14 (14.29%)	2	0/39 (0.00%)	0	1/22 (4.55%)	1
Upper respiratory tract infection † 1	3/14 (21.43%)	3	1/39 (2.56%)	1	1/22 (4.55%)	1
Urinary tract infection † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	1/22 (4.55%)	1
Injury, poisoning and procedural complications
Contrast media reaction † 1	1/14 (7.14%)	2	0/39 (0.00%)	0	0/22 (0.00%)	0
Infusion related reaction † 1	2/14 (14.29%)	5	0/39 (0.00%)	0	0/22 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/14 (7.14%)	1	3/39 (7.69%)	4	0/22 (0.00%)	0
Aspartate aminotransferase increased † 1	0/14 (0.00%)	0	3/39 (7.69%)	4	0/22 (0.00%)	0
Blood creatinine increased † 1	1/14 (7.14%)	3	3/39 (7.69%)	5	1/22 (4.55%)	1
Blood urea increased † 1	0/14 (0.00%)	0	4/39 (10.26%)	4	0/22 (0.00%)	0
C-reactive protein increased † 1	0/14 (0.00%)	0	3/39 (7.69%)	3	1/22 (4.55%)	1
Neutrophil count decreased † 1	2/14 (14.29%)	6	3/39 (7.69%)	4	2/22 (9.09%)	5
Platelet count decreased † 1	1/14 (7.14%)	3	2/39 (5.13%)	8	0/22 (0.00%)	0
Weight decreased † 1	0/14 (0.00%)	0	3/39 (7.69%)	4	2/22 (9.09%)	3
White blood cell count decreased † 1	1/14 (7.14%)	4	1/39 (2.56%)	4	0/22 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	2/14 (14.29%)	3	14/39 (35.90%)	45	12/22 (54.55%)	19
Dehydration † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	1/22 (4.55%)	1
Dyslipidaemia † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Hyperglycaemia † 1	2/14 (14.29%)	3	1/39 (2.56%)	1	2/22 (9.09%)	4
Hypocalcaemia † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Hypokalaemia † 1	1/14 (7.14%)	2	3/39 (7.69%)	3	1/22 (4.55%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/14 (7.14%)	1	2/39 (5.13%)	3	2/22 (9.09%)	2
Back pain † 1	1/14 (7.14%)	1	3/39 (7.69%)	3	2/22 (9.09%)	2
Bone pain † 1	1/14 (7.14%)	1	3/39 (7.69%)	3	2/22 (9.09%)	2
Muscle spasms † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Musculoskeletal chest pain † 1	1/14 (7.14%)	1	5/39 (12.82%)	6	1/22 (4.55%)	1
Musculoskeletal pain † 1	3/14 (21.43%)	3	7/39 (17.95%)	11	4/22 (18.18%)	6
Osteoarthritis † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Pain in extremity † 1	2/14 (14.29%)	3	3/39 (7.69%)	4	1/22 (4.55%)	1
Spinal pain † 1	0/14 (0.00%)	0	2/39 (5.13%)	4	0/22 (0.00%)	0
Nervous system disorders
Dizziness † 1	1/14 (7.14%)	1	6/39 (15.38%)	12	1/22 (4.55%)	1
Dysaesthesia † 1	1/14 (7.14%)	2	0/39 (0.00%)	0	0/22 (0.00%)	0
Dysgeusia † 1	1/14 (7.14%)	2	2/39 (5.13%)	2	1/22 (4.55%)	1
Headache † 1	3/14 (21.43%)	5	8/39 (20.51%)	17	2/22 (9.09%)	2
Hypoaesthesia † 1	0/14 (0.00%)	0	1/39 (2.56%)	1	2/22 (9.09%)	3
Neurotoxicity † 1	0/14 (0.00%)	0	7/39 (17.95%)	9	0/22 (0.00%)	0
Paraesthesia † 1	3/14 (21.43%)	5	4/39 (10.26%)	4	1/22 (4.55%)	1
Paresis † 1	1/14 (7.14%)	1	1/39 (2.56%)	1	0/22 (0.00%)	0
Presyncope † 1	1/14 (7.14%)	2	1/39 (2.56%)	1	1/22 (4.55%)	1
Somnolence † 1	1/14 (7.14%)	1	1/39 (2.56%)	1	0/22 (0.00%)	0
Tremor † 1	0/14 (0.00%)	0	2/39 (5.13%)	4	0/22 (0.00%)	0
Psychiatric disorders
Anxiety † 1	0/14 (0.00%)	0	3/39 (7.69%)	3	2/22 (9.09%)	2
Depression † 1	1/14 (7.14%)	2	1/39 (2.56%)	1	1/22 (4.55%)	1
Insomnia † 1	5/14 (35.71%)	6	4/39 (10.26%)	5	3/22 (13.64%)	4
Renal and urinary disorders
Nephrolithiasis † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Reproductive system and breast disorders
Menstruation irregular † 1	0/7 (0.00%)	0	1/15 (6.67%)	1	0/8 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/14 (21.43%)	4	8/39 (20.51%)	19	3/22 (13.64%)	3
Dysphonia † 1	0/14 (0.00%)	0	4/39 (10.26%)	4	4/22 (18.18%)	4
Dyspnoea † 1	0/14 (0.00%)	0	12/39 (30.77%)	16	7/22 (31.82%)	9
Epistaxis † 1	1/14 (7.14%)	2	5/39 (12.82%)	5	0/22 (0.00%)	0
Hiccups † 1	2/14 (14.29%)	5	1/39 (2.56%)	1	2/22 (9.09%)	3
Nasal congestion † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Oropharyngeal pain † 1	2/14 (14.29%)	2	0/39 (0.00%)	0	1/22 (4.55%)	1
Pleural effusion † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Productive cough † 1	0/14 (0.00%)	0	0/39 (0.00%)	0	4/22 (18.18%)	4
Rhinitis allergic † 1	1/14 (7.14%)	1	1/39 (2.56%)	1	0/22 (0.00%)	0
Sneezing † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia † 1	4/14 (28.57%)	4	5/39 (12.82%)	5	0/22 (0.00%)	0
Angioedema † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Dermatitis acneiform † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Dry skin † 1	2/14 (14.29%)	2	3/39 (7.69%)	3	1/22 (4.55%)	2
Eczema † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	3/22 (13.64%)	3
Erythema † 1	1/14 (7.14%)	1	2/39 (5.13%)	2	1/22 (4.55%)	1
Erythema multiforme † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	1/22 (4.55%)	1
Hyperhidrosis † 1	2/14 (14.29%)	2	2/39 (5.13%)	2	1/22 (4.55%)	1
Nail disorder † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Night sweats † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	1/22 (4.55%)	1
Pruritus † 1	2/14 (14.29%)	3	1/39 (2.56%)	1	4/22 (18.18%)	4
Rash † 1	2/14 (14.29%)	3	4/39 (10.26%)	4	2/22 (9.09%)	2
Skin discolouration † 1	1/14 (7.14%)	2	0/39 (0.00%)	0	0/22 (0.00%)	0
Skin disorder † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Skin lesion † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	0/22 (0.00%)	0
Surgical and medical procedures
Catheterisation venous † 1	1/14 (7.14%)	1	0/39 (0.00%)	0	0/22 (0.00%)	0
Vascular disorders
Circulatory collapse † 1	1/14 (7.14%)	2	0/39 (0.00%)	0	0/22 (0.00%)	0
Haematoma † 1	2/14 (14.29%)	2	4/39 (10.26%)	4	0/22 (0.00%)	0
Hypertension † 1	3/14 (21.43%)	7	3/39 (7.69%)	4	1/22 (4.55%)	1
Hypertensive crisis † 1	1/14 (7.14%)	1	2/39 (5.13%)	2	0/22 (0.00%)	0
Hypotension † 1	2/14 (14.29%)	2	1/39 (2.56%)	1	1/22 (4.55%)	1
Phlebitis † 1	0/14 (0.00%)	0	2/39 (5.13%)	2	1/22 (4.55%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.1

Limitations and Caveats

Enrollment was halted on 25 October 2012 due to a numerical imbalance in events of thromboembolic nature between the experimental arm and the control arm.

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wehler T, Thomas M, Schumann C, Bosch-Barrera J, Vinolas Segarra N, Dickgreber NJ, Dalhoff K, Sebastian M, Corral Jaime J, Alonso M, Hynes SM, Lin J, Hurt K, Bence Lin A, Calvo E, Paz-Ares L. A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non-small cell lung cancer. Lung Cancer. 2017 Jun;108:212-216. doi: 10.1016/j.lungcan.2017.03.001. Epub 2017 Mar 6.

Calvo E, Chen VJ, Marshall M, Ohnmacht U, Hynes SM, Kumm E, Diaz HB, Barnard D, Merzoug FF, Huber L, Kays L, Iversen P, Calles A, Voss B, Lin AB, Dickgreber N, Wehler T, Sebastian M. Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Invest New Drugs. 2014 Oct;32(5):955-68. doi: 10.1007/s10637-014-0114-5. Epub 2014 Jun 20.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01139775
• Other Study ID Numbers: 13797; I2I-MC-JMMG ( Other Identifier: Eli Lilly and Company )
• First Submitted: June 1, 2010
• First Posted: June 9, 2010
• Results First Submitted: February 17, 2018
• Results First Posted: May 18, 2018
• Last Update Posted: May 18, 2018