A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

Inclusion Criteria

• Male or female subjects ≥ 18 and ≤ 75 years of age
• Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection and treatment with investigational products prior to undergoing any study procedures
• Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
• Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
• Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:
• Nitrosoureas: 6 weeks
• Other cytotoxic agents: 4 weeks
• Anti-angiogenic agents including bevacizumab: 4 weeks
• Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks
• Experimental immunotherapies: 3 months
• Vaccine based therapy: 3 months
• Able to undergo standard MRI scans with contrast agent
• Karnofsky Performance Status ≥ 70
• Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
• Hemoglobin ≥ 9 g/L
• Lymphocytes > 500/ mm3
• Absolute Neutrophil Count ≥ 1500/ mm3
• Platelets ≥ 100,000/ mm3
• Serum creatinine ≤ 1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5 × ULN
• Total bilirubin < 1.5 x ULN
• International Normalized Ratio (INR) and activated Partial Thromboplastin Time [PTT] within normal institutional limits
• Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria

• Radiotherapy within 4 weeks or less prior to starting first veledimex dose
• Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
• Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
• Use of systemic antibacterials, antifungals or antivirals for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is permitted perioperatively.
• Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
• Other concurrent clinically active malignant disease, requiring treatment, with the exception of non-melanoma cancers of the skin or carcinoma in-situ of the cervix or non-metastatic prostate cancer.
• Nursing or pregnant females
• Prior exposure to veledimex
• Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing
• Presence of any contra-indication for a neurosurgical procedure
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator or medical monitor, jeopardize the safety of a subject and/or their compliance with the protocol.