we evaluated the efficacy of combination enzastaurin ly317615 and bevacizumab for recurrent malignant gliomas and explored serologic correlates we enrolled 81 patients with glioblastomas gbm n 40 and anaplastic gliomas ag n 41 patients received enzastaurin as a loading dose of 1125 mg followed by 500 or 875 mg daily for patients on non enzyme inducing or enzyme inducing antiepileptics respectively patients received bevacizumab 10 mg kg intravenously biweekly clinical evaluations were repeated every 4 weeks magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset phosphorylated glycogen synthase kinase gsk 3 levels from peripheral blood mononuclear cells pbmcs were checked with each mri median overall survival was 7 5 and 12 4 months for glioblastomas and anaplastic glioma cohorts with median progression free survivals of 2 0 and 4 4 months respectively of gbm patients 3 40 7 5 were not evaluable while 8 37 22 had partial or complete response and 20 37 54 had stable disease for 2 months of the 39 evaluable ag patients 18 46 had an objective response and 16 41 had stable disease for 2 months the most common grade 3 toxicities were lymphopenia 15 hypophosphatemia 8 8 and thrombotic events 7 5 two 2 5 gbm patients died suddenly another death 1 3 occurred from intractable seizures phosphorylated gsk 3 levels from pbmcs did not correlate with treatment response a minimally important improvement in health related quality of life was self reported in 7 9 24 29 2 37 5 early response based on levin criteria was significantly associated with significantly longer progression free survival for glioblastomas enzastaurin ly317615 in combination with bevacizumab for recurrent malignant gliomas is well tolerated with response and progression free survival similar to bevacizumab monotherapy.