A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only

PFS time is the elapsed time from the date of randomization to the first date of objectively-determined PD or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (other than enzastaurin maintenance therapy) prior to objectively determined disease progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of subsequent therapy.

Time frame: Randomization to measured PD or death from any cause (up to 55 months)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 34 and 21 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Duration of response (DOR) either CR or CRu: Elapsed time from date CR or CRu criteria met to first objectively-determined PD. For responding participants (pts) who died without PD and pts not known to have died as of data cut-off date, who did not have PD, DOR censored at date of last objective progression-free disease assessment. For responding pts who received subsequent systemic anticancer therapy (other than enzastaurin maintenance therapy) prior to PD, DOR was censored at date of last objective progression-free disease assessment prior to subsequent therapy. CR and CRu defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

Time frame: Time of response to PD (up to 55 months)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who achieved CR or CRu. A total of 22 and 9 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

EFS is the elapsed time from the date of randomization to the first date of objectively-determined PD, institution of a new anticancer treatment (other than maintenance therapy), or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date, who did not have objectively determined disease progression, and who were not treated with a new anticancer treatment, EFS was censored at the date of the last objectively determined disease-free assessment.

Time frame: Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 31 and 20 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

OS is the elapsed time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date or last date known to be alive, whichever was later.

Time frame: Baseline to death from any cause (up to 55 months)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 42 and 28 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Data presented are the number of participants who experienced at least 1 TEAE, Grade 3 or 4 Common Terminology Criteria for Adverse Events (CTCAE), serious adverse event (SAE), as well as the number of participants who discontinued due to an adverse event (AE) or SAE, who died on therapy, died within 30 days post treatment or within 60 days of first dose. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Time frame: First dose through 30 days post study treatment discontinuation (up to 56 months)

Population: Safety Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen.

PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. Percentage of participants alive progression-free at Year 2=(Number of participants alive progression free at Year 2)/(Number of participants assessed)\*100.

Time frame: Randomization to measured PD (up to Year 2)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement.

The percentage of participants with a PET-negative scan=(Number of participants who had a PET-negative scan at Cycle 6)/(Number of participants who had a PET-positive scan at baseline)\*100.

Time frame: Cycle 6 (21 days/cycle)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had a PET-positive scan at baseline.

CR, CRu, and PR were defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. PR is a 50% decrease in the sum of the products of diameters for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. The percentage of participants with complete response (CR/CRu) and objective response (Cr/CRu/PR)=(Number of participants whose best overall response was CR/CRu or Cr/CRu/PR)/(Number of participants treated)\*100.

Time frame: Baseline through long-term follow-up (up to 2 years post last dose)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement.

Lesion response was assessed according to International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. Percentage of participants with CR/CRu and/or PET-negative scan=(Number of participants with complete response and/or PET-negative scan at Cycle 6)/(Number of participants with a PET-positive scan at baseline)\*100.

Time frame: Cycle 6 (21 days/cycle)

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen, who had a PET-positive scan at baseline.

Reported is PFS of participants (pts) with high or low biomarker expression levels. PFS: time from randomization to first date of PD/death from any cause. PD assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new/increased lymph node/masses and reappearance of bone marrow infiltrate. For pts who had subsequent anticancer therapy, PFS censored at date of last assessment prior to subsequent therapy. Biomarkers and number of pts censored: EIF4EBP1 Cytoplasm (C) 4,3,7,3; EIF4EBP1 Nucleus (N) 0,2,11,4; EIF4E C 5,2,6,4; EIF4E N 0,0,11,6; HDAC2 N 5,1,5,5; PCREB N 5,3,6,4; PEIF3746 C 4,2,7,4; PEIF3746 N 5,2,6,4; PEIFS209 C 5,2,5,4; PEIFS65 N 7,2,4,4; PEIFT70 C 5,2,6,4; PEIFT70 N 6,4,5,2; P GSK3B C 7,3,4,3; PKCb2 C 4,3,7,3; PS6 C 9,4,1,1; PTEN C 5,2,6,4; PTEN N 3,0,8,6. Correlation of biomarkers with PFS (statistical analyses) reported if high expression groups combined and low expression groups combined each had ≥10 pts.

Time frame: Randomization to measured PD or death from any cause (up to 55 months)]

Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen, who had at least 1 post-baseline efficacy measurement and had a reported value for the biomarker measure of interest.