Trial Outcomes & Findings for First Line Chemotherapy Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00308750)

Last Updated: 2021-05-13

Results Overview

Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

218 participants

Primary outcome timeframe

Baseline to measured PD up to 22.3 months

Results posted on

2021-05-13

Participant Flow

Presented in the participant flow are the reasons participants discontinued from study treatment.

Participant milestones

Participant milestones
Measure	Enzastaurin/Pemetrexed/Carboplatin Enzastaurin loading dose of 1125 milligrams (mg) or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 milligrams per square meter (mg/m\^2) and carboplatin \[area under the curve (AUC)\] 6 milligrams\minutes per milliliter (mg\min/mL) as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Overall Study STARTED	72	74	72
Overall Study Received at Least 1 Dose of Study Drug	67	72	70
Overall Study COMPLETED	0	34	23
Overall Study NOT COMPLETED	72	40	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzastaurin/Pemetrexed/Carboplatin Enzastaurin loading dose of 1125 milligrams (mg) or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 milligrams per square meter (mg/m\^2) and carboplatin \[area under the curve (AUC)\] 6 milligrams\minutes per milliliter (mg\min/mL) as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Overall Study Adverse Event	9	9	13
Overall Study Withdrawal by Subject	6	2	3
Overall Study Physician Decision	3	4	3
Overall Study Sponsor Decision	1	0	0
Overall Study Disease Progression	47	24	28
Overall Study Unrelated Complication	3	0	1
Overall Study Death	1	0	1
Overall Study Protocol Violation	1	0	0
Overall Study New Primary Disease Identified	1	1	0

Baseline Characteristics

First Line Chemotherapy Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzastaurin/Pemetrexed/Carboplatin n=72 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=74 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=72 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Total n=218 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 9.8 • n=5 Participants	64.0 years STANDARD_DEVIATION 10.0 • n=7 Participants	64.0 years STANDARD_DEVIATION 9.1 • n=5 Participants	64.4 years STANDARD_DEVIATION 9.8 • n=4 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	33 Participants n=7 Participants	30 Participants n=5 Participants	94 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	41 Participants n=7 Participants	42 Participants n=5 Participants	124 Participants n=4 Participants
Race/Ethnicity, Customized African	5 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	62 Participants n=5 Participants	63 Participants n=7 Participants	63 Participants n=5 Participants	188 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	5 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	72 Participants n=5 Participants	74 Participants n=7 Participants	72 Participants n=5 Participants	218 Participants n=4 Participants
Disease Stage at Study Entry Stage IIIB	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Disease Stage at Study Entry Stage IV	66 Participants n=5 Participants	69 Participants n=7 Participants	66 Participants n=5 Participants	201 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to measured PD up to 22.3 months

Population: All randomized participants. Twenty (20) participants in Enzastaurin/Pemetrexed/Carboplatin group, 15 participants in Pemetrexed/Carboplatin group, and 17 participants in Docetaxel/Carboplatin group were censored for analysis.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=52 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=59 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=55 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Time to Disease Progression	4.6 months Interval 3.2 to 6.7	6.0 months Interval 4.6 to 6.5	4.1 months Interval 2.6 to 6.3

SECONDARY outcome

Timeframe: Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up

Population: Zero participants were analyzed due to insufficient samples being collected.

As specified in the protocol, tumor biomarker samples were collected from participants on the pemetrexed arms only but were not intended to be analyzed at the individual study level.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: Zero participants were analyzed due to insufficient samples being collected.

Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up

Population: Randomized participants who received at least 1 dose of study drug.

Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=67 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=72 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=70 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Number of Participants With Adverse Events (AEs) or Deaths SAEs	35 Participants	20 Participants	26 Participants
Number of Participants With Adverse Events (AEs) or Deaths Deaths Due to AEs	3 Participants	5 Participants	4 Participants
Number of Participants With Adverse Events (AEs) or Deaths AEs	63 Participants	70 Participants	69 Participants

SECONDARY outcome

Timeframe: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]

Population: Randomized participants with non-missing FACT-L data both at baseline and at the specified cycle.

The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to "worst quality of life" to 136 equal to "best quality of life". The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=45 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=50 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=42 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 1 (Week 3)	-3.98 units on a scale Standard Error 1.86	1.12 units on a scale Standard Error 1.78	-3.33 units on a scale Standard Error 1.88
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 2 (Week 6)	-3.25 units on a scale Standard Error 2.19	-1.54 units on a scale Standard Error 2.08	-2.16 units on a scale Standard Error 2.42
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 3 (Week 9)	0.39 units on a scale Standard Error 2.30	0.64 units on a scale Standard Error 2.25	-1.93 units on a scale Standard Error 2.49
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 4 (Week 12)	0.31 units on a scale Standard Error 2.47	3.54 units on a scale Standard Error 2.23	-0.81 units on a scale Standard Error 2.50
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 5 (Week 15)	1.89 units on a scale Standard Error 2.95	-0.26 units on a scale Standard Error 2.57	-4.69 units on a scale Standard Error 2.79
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale Cycle 6 (Week 18)	7.38 units on a scale Standard Error 3.54	-0.83 units on a scale Standard Error 2.84	3.38 units on a scale Standard Error 3.54

SECONDARY outcome

Timeframe: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]

Population: Randomized participants with non-missing FACT-Taxane data both at baseline and at the specified cycle.

The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 "worst quality of life" to 172 "best quality of life". The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=45 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=50 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=43 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 1 (Week 3)	-3.16 units on a scale Standard Error 2.20	-0.78 units on a scale Standard Error 2.08	-2.17 units on a scale Standard Error 2.20
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 2 (Week 6)	-6.22 units on a scale Standard Error 2.90	-5.66 units on a scale Standard Error 2.76	-3.13 units on a scale Standard Error 3.16
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 3 (Week 9)	-1.89 units on a scale Standard Error 3.35	-1.52 units on a scale Standard Error 3.32	-4.40 units on a scale Standard Error 3.62
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 4 (Week 12)	-2.28 units on a scale Standard Error 3.65	-0.77 units on a scale Standard Error 3.29	-2.58 units on a scale Standard Error 3.74
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 5 (Week 15)	-2.52 units on a scale Standard Error 3.71	-3.11 units on a scale Standard Error 3.24	-7.74 units on a scale Standard Error 3.51
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale Cycle 6 (Week 18)	2.77 units on a scale Standard Error 3.93	-2.81 units on a scale Standard Error 3.26	-0.34 units on a scale Standard Error 4.06

SECONDARY outcome

Timeframe: Baseline to date of death from any cause up to 35 months

Population: All randomized participants. Sixteen (16) participants in Enzastaurin/Pemetrexed/Carboplatin group, 20 participants in Pemetrexed/Carboplatin group, and 19 participants in Docetaxel/Carboplatin group were censored for analysis.

OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=56 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=54 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=53 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Overall Survival (OS)	7.2 months Interval 5.7 to 11.2	12.7 months Interval 9.3 to 17.0	9.2 months Interval 5.9 to 10.7

SECONDARY outcome

Timeframe: Baseline to measured PD up to 22.3 months

Population: All randomized participants.

Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or PR were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=72 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=74 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=72 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response]	9 Participants	16 Participants	19 Participants

SECONDARY outcome

Timeframe: Date of first response to the date of progression or death due to any cause up to 22.3 months

Population: All randomized participants. 63 participants in Enzastaurin/Pemetrexed/Carboplatin group, 58 participants in Pemetrexed/Carboplatin group, and 53 participants in Docetaxel/Carboplatin group were censored for analysis.

The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=9 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=16 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=19 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Duration of CR or PR (Duration of Response)	7.4 months Interval 3.7 to 8.8	9.3 months Interval 5.7 to 14.8	5.8 months Interval 3.3 to 11.3

SECONDARY outcome

Timeframe: Baseline to stopping treatment up to 14.1 months

Population: All randomized participants. Thirty four (34) participants in Pemetrexed/Carboplatin group and 23 participants in Docetaxel/Carboplatin group were censored for analysis. No participants were censored in Enzastaurin/Pemetrexed/Carboplatin group.

TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.

Outcome measures

Outcome measures
Measure	Enzastaurin/Pemetrexed/Carboplatin n=38 Participants Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=51 Participants Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=72 Participants Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Time-to-Treatment Failure (TTF)	2.6 months Interval 1.7 to 3.7	3.8 months Interval 2.8 to 5.1	2.6 months Interval 1.3 to 3.7

Adverse Events

Enzastaurin/Pemetrexed/Carboplatin

Serious events: 35 serious events

Other events: 63 other events

Deaths: 0 deaths

Pemetrexed/Carboplatin

Serious events: 20 serious events

Other events: 70 other events

Deaths: 0 deaths

Docetaxel/Carboplatin

Serious events: 26 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Enzastaurin/Pemetrexed/Carboplatin n=67 participants at risk Enzastaurin loading dose of 1125 mg or 1200 mg on Day -7 (pre-chemotherapy) followed by 500 mg administered once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed/Carboplatin n=72 participants at risk Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel/Carboplatin n=70 participants at risk Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Blood and lymphatic system disorders Febrile neutropenia	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	8.6% 6/70 • Number of events 8 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Cardiac disorders Arrhythmia	4.5% 3/67 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Cardiac disorders Cardio-respiratory arrest	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Cardiac disorders Myocardial infarction	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Cardiac disorders Pericardial effusion	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Abdominal pain	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Caecitis	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Diarrhoea	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	4.3% 3/70 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Enteritis	3.0% 2/67 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Nausea	1.5% 1/67 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Rectal haemorrhage	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Stomatitis	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Vomiting	1.5% 1/67 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Chest pain	4.5% 3/67 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Disease progression	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Fatigue	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Localised oedema	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Oedema due to cardiac disease	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Pain	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
General disorders Pyrexia	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Infections and infestations Abdominal infection	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Infections and infestations Cellulitis	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Infections and infestations Pneumonia	10.4% 7/67 • Number of events 8 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	4.2% 3/72 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	2.9% 2/70 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Infections and infestations Sepsis	3.0% 2/67 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	5.7% 4/70 • Number of events 4 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Injury, poisoning and procedural complications Fracture	3.0% 2/67 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	2.8% 2/72 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Aspartate aminotransferase	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Blood bilirubin	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Blood calcium decreased	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/72 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Blood creatinine	0.00% 0/67 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Blood potassium decreased	4.5% 3/67 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Blood sodium decreased	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	1.4% 1/70 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Haemoglobin	6.0% 4/67 • Number of events 4 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	4.2% 3/72 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	2.9% 2/70 • Number of events 2 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Neutrophil count	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	4.3% 3/70 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations Platelet count	1.5% 1/67 • Number of events 1 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Investigations White blood cell count	4.5% 3/67 • Number of events 3 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/72 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.	0.00% 0/70 Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.