Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer

Response rate was defined as percentage of responders (best study response recorded as CR or PR) from the qualified number of participants for tumor response analysis. Response defined using Response Evaluation Criteria In Solid Tumors (RECIST, v1.0) criteria: CR was disappearance of all target lesions for at least 4 weeks. PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.

Percentage of participants was calculated as: (The number of responders with CR or PR/ The number of participants qualified for tumor response analysis) × 100.

PFS was defined as the time from the date of randomization to the first date of documented progressive disease (PD) or death due to any cause, whichever occurred first. PFS was censored at the date of the last assessment visit for participants who were still alive at data cut-off and who had not had documented progressive disease. Participants who started a new treatment before progression were censored as of the date of the start of new treatment.

The duration of a complete response (CR) or partial response (PR) was defined, using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, as the time from first objective status assessment of CR or PR to the first time of disease progression or death as a result of any cause. 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 LD. Duration of response was censored at the date of the last assessment visit for responders who were still alive at data cut-off and had no documented progressive disease (PD).

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180. The Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

OS was the duration from randomization to death from any cause. For participants who were alive at data cut-off, OS was censored at the last contact. Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 [metabolite]): those participants below the median and those participants above the median [2786.042 nanomoles per /liter (nmol/l)]. The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only treatment group.

The overall disease control rate was calculated as percent of participants with overall response of complete response (CR), partial response (PR) or stable disease (SD) over number of per-protocol population. Using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR: disappearance of all target and non-target lesions; PR: as at least a 30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD) was defined as at least 20% increase in sum of LD of target lesions; SD: small changes that did not meet above criteria.

Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 [metabolite]): participants below the median and participants above the median [2754.521 nanomoles per liter (nmol/l)].

The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only group.

CA19-9 is a tumor biomarker which was measured in the blood to assess the effect of treatment with enzastaurin.

Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). Participants who died due to progressive disease (PD), AEs while on treatment or died during the 30 day post-treatment are included. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.