Open-label Study Investigating of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma

A Phase II Open-label Study Investigating the Efficacy, Safety and Pharmacokinetic Properties of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma

This is a phase II open-label study investigating the efficacy, safety and pharmacokinetic(PK) properties of OKN-007 combined with temozolomide(TMZ) in patients with recurrent glioblastoma(GBM). All patients will have been previously treated with the standard-of-care treatment which includes surgical resection, radiation and chemotherapy, and in some cases treatment for recurrent disease. Patients with unequivocal recurrence (first or greater) established by MRI and meeting inclusion and exclusion criteria, will be eligible for OKN-007 treatment on this protocol.

Inclusion Criteria:

1. Confirmed Glioblastoma based on histopathology or molecular profile analysis (WHO Grade IV), following primary treatment with TMZ and radiotherapy (minimum of 50 Gy) and at least two cycles of maintenance TMZ (5 days of a 28 day cycle) as first-line or second-line treatment with another treatment regimen, excluding bevacizumab.

2. Patients must have medical records available documenting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status analysis or must have tumor tissue samples available from prior GBM surgery or open biopsy for MGMT status determination.

3. For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI. These patients must have at least one measurable lesion.

4. Patients with recent resection of recurrent viable tumor are eligible following post-operative MRI perfusion scan with or without measurable lesions.

5. No more than two prior lines of therapy for glioblastoma. Any second-line therapy is acceptable, excluding bevacizumab as second line.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

7. Full recovery (≤ grade 1) from the toxic effects.

8. Adequate renal, liver and bone marrow function:

   • Hemoglobin >9.0 g/dL
   • Leukocytes >3,000/mcL
   • Absolute neutrophil count >1,500/mcL
   • Platelets >100,000/mcL
   • Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
   • AST (SGOT) / ALT (SGPT) ≤2.5 × ULN
   • Creatinine clearance ≥ 60 mL/min

9. Patients must be ≥18 years of age

Exclusion Criteria:

1. Early discontinuation of TMZ in prior line due to treatment related Adverse events (AEs).
2. Second primary malignancy expected to require treatment within a 6 month period (except adequately treated basal cell carcinoma of the skin).
3. Have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study entry.
4. Have received chemotherapeutic agents (including temozolomide) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study entry
5. Serious concomitant systemic disorders
6. Patients with abnormal sodium, potassium, or creatinine levels ≥ grade 2.
7. Patients with prothrombin time/partial thromboplastin time (PT/PTT) or International normalized ratio (INR) above the ULN.
8. Inability to comply with protocol or study procedures.
9. Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis. (Past treatment with bevacizumab for tumor necrosis is acceptable).
10. Patients receiving or planning to initiate treatment with the tumor treating fields device (Optune®) (Optune® prior to enrollment is permitted).