This is a study of oral LY2157299 as monotherapy and in combination with lomustine in participants with recurrent malignant glioma.

Inclusion Criteria:

• Have given written informed consent

• Have histological or cytological evidence of relapsed malignant glioma (such as glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma) for which no treatment of higher priority exists

  • Available baseline tumor specimen is required prior to considering participant to be enrolled. The original diagnostic tumor tissue is sufficient for this inclusion criteria, but where possible, freshly obtained tumor biopsy material may be obtained
  • Measurable disease to allow assessment of tumor response based on radiographic assessment following Macdonald criteria and Response Evaluation Criteria In Solid Tumors (RECIST)

• Have sufficient hepatic, renal, and hematological function

• Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy or other investigational therapy for at least 30 days prior to study enrollment and recovered from the acute effects of therapy

• Able to swallow tablets and capsules

• For females, reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method (including intrauterine or barrier devices) during and for 3 to 6 months after the study

• Male participants must be willing to use contraception during and for 3 to 6 months after the study

Exclusion Criteria:

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

• Have moderate or severe cardiac disease:

  • Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension
  • Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks, ventricular hypertrophy, or recent myocardial infarction)
  • Have major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of normal)
  • Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast)

• Have current acute or chronic leukemia

• Women who are pregnant or lactating

• Have received prior nitrosourea (including lomustine) therapy