A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma

In arm A, patients who are candidates for surgical resection will receive BBI608 as
monotherapy prior to resection, followed by post-operative BBI608 administered in combination
with temozolomide. In arm B, patients who are not candidates for surgical resection will
receive BBI608 administered orally, daily, in combination with temozolomide.

In the phase 1/DLT cohort portion of this study, pharmacokinetics will be evaluated for both
arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical
resection.

Major Eligilbility Criteria

1. Signed written informed consent must be obtained and documented according to
International Conference on Harmonisation (ICH) and local regulatory requirements.

2. A histologically confirmed supratentorial glioblastoma (GBM) at first
recurrence/progression (except for transformation from previous low grade glioma)
following standard front-line therapy, for which treatment with temozolomide (TMZ)
would be acceptable as determined by the Investigator

3. Previously received standard front-line GBM treatment including maximal surgical
resection followed by external beam radiation therapy.

4. Patients may or may not be candidates for repeat surgical resection of the
recurrent/progressed GBM.

5. Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a
minimum of 12 weeks following completion of chemoradiation or radiation therapy.

6. Patients must have measurable or non-measurable disease by response assessment in
neuro-oncology (RANO) criteria

7. ≥18 years of age.

8. Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1