Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Participants With Non-Small Cell Lung Cancer Who Have Not Been Previously Treated With Chemotherapy

• enzastaurin (Drug), also known as LY317615: 1125 milligram (mg) loading dose then 500 mg, oral, daily until disease progression
• pemetrexed (Drug), also known as LY231514, Alimta: 500 milligrams per square meter (mg/m\^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles
• carboplatin (Drug): Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles
• bevacizumab (Drug): 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles
• Placebo (Drug): oral, daily

Primary outcomes

• Progression-Free Survival (PFS) [Randomization to measured PD or death from any cause up to 12.2 months]: PFS was defined as the time from date of randomization to the first observation of progressive disease (PD) or death due to any cause. For participants not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to objective disease progression or death, PFS was censored at the date of the last objective progression-free assessment prior to the initiation of post-discontinuation anticancer therapy.

Secondary outcomes

• Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) [Randomization to measured progressive disease or death from any cause up to 12.2 months]: Tumor response rate was defined as number of participants with overall best response of CR or PR over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case, no new lesions may have appeared. Percentage of participants was calculated as: (number of participants with CR or PR/ number of participants qualified for tumor response analysis) × 100.
• Overall Survival (OS) [Randomization to date of death up to 14.3 months]: OS was defined as the time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data cutoff, OS was censored at the last contact date.
• Time to Progressive Disease (TTPD) [Randomization to measured PD or death from any cause up to 12.2 months]: TTPD was defined as the time from the date of randomization until the first date of objectively determined progressive disease (PD). For participants who died without objective PD (including death from study disease), TTPD was censored at the date of the last objective progression-free disease assessment. For participants not known to have died as of the data cutoff and did not have PD, TTPD was censored at the date of the last objective progression-free disease assessment.
• Duration of Response (DoR) [Time of response to disease progression or death from any cause up to 12.2 months]: The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target lesions and PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum of LDs. For participants who died without progressive disease or who were alive, DoR was censored at the last contact of progression free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to PD, DoR was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. Due to early study closure, DoR was not analyzed.
• Pharmacology Toxicity and Adverse Events (AEs) [Randomization up to 14.3 months and 30-day follow-up]: Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to progressive disease (PD) or an AE while on treatment and or died during the 30 day post-treatment follow-up are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* participants or their legal representative must have signed an informed consent document for clinical research
* have laboratory confirmed diagnosis of advanced, nonsquamous cell non-small cell lung cancer (NSCLC) (Stage IIIB or IV disease) which is not curable
* have not received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for advanced NSCLC, prior radiation therapy is allowed to less than 25% of the bone marrow
* have measurable disease
* have adequate organ function and estimated life expectancy of 12 weeks

Exclusion Criteria:

* have known central nervous system (CNS) disease; major surgery within 28 days; minor surgery within 7 days; serious concomitant systemic disorder; serious cardiac condition; have a serious, nonhealing wound, ulcer, or bone fracture
* have received treatment within the last 30 days with any drug that has not received regulatory approval for any indication at the time of study entry
* have previously received treatment with enzastaurin, pemetrexed, or bevacizumab
* are pregnant or breast-feeding
* are unable to swallow tablets

Participant flow

Outcome results

• Progression-Free Survival (PFS) (Primary), Number, months: Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin 3.5 (2.0 to 5.8); Pemetrexed + Carboplatin + Bevacizumab + Placebo 4.3 (2.5 to 5.8) (p 0.469)
• Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) (Secondary), Number, percentage of participants: Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin 20.0 (2.5 to 37.5); Pemetrexed + Carboplatin + Bevacizumab + Placebo 30.0 (9.9 to 50.1) (p 0.462)
• Overall Survival (OS) (Secondary), Median, months: Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin 9.1 (7.8 to NA); Pemetrexed + Carboplatin + Bevacizumab + Placebo 7.6 (4.2 to NA) (p 0.492)
• Time to Progressive Disease (TTPD) (Secondary), Median, Months: Enzastaurin + Pemetrexed + Carboplatin + Bevacizumab 4.3 (1.7 to 5.8); Pemetrexed + Carboplatin + Bevacizumab + Placebo 4.8 (3.0 to 7.2)
• Duration of Response (DoR) (Secondary), Median, Months: Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin 4.7 (2.8 to NA); Pemetrexed + Carboplatin + Bevacizumab + Placebo 3.5 (1.3 to NA)
• Pharmacology Toxicity and Adverse Events (AEs) (Secondary), Count of participants, Participants: Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin 19; Pemetrexed + Carboplatin + Bevacizumab + Placebo 20

Adverse events

Time frame: Randomization up to 14.3 months and 30-day follow-up

Serious adverse events by term

Other adverse events by term

42 more terms not shown.

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