A Study of Ad-RTS-hIL-12 With Veledimex in Combination With Nivolumab in Subjects With Glioblastoma; a Substudy to ATI001-102

Inclusion Criteria:

Male or female subject ≥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 specific procedures
Histologically confirmed supratentorial glioblastoma
Evidence of tumor recurrence/progression by magnetic resonance imaging (MRI) according to response assessment in neuro-oncology (RANO) criteria after standard initial therapy

Previous standard-of-care antitumor treatment including surgery and/or biopsy and chemoradiation. At the time of registration, subjects must have recovered from the toxic effects of previous treatments as determined by the treating physician. The washout periods from prior therapies are intended as follows: (windows other than what is listed below should be allowed only after consultation with the Medical Monitor)

Nitrosureas: 6 weeks
Other cytotoxic agents: 4 weeks
Antiangiogenic agents, including bevacizumab: 4weeks
Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
Vaccine-based therapy: 3 months
Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
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 upper limit of normal (ULN)
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5 x ULN
Total bilirubin < 1.5 x ULN
International normalized ratio (INR) and aPTT within normal institutional limits
Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate <5% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential (perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) must have a negative pregnancy test at screening.
Normal cardiac and pulmonary function as evidenced by a normal ECG and peripheral oxygen saturation (SpO2) ≥90% by pulse oximetry

Exclusion Criteria:

Previous treatment with inhibitors of immunocheckpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) or other agents specifically targeting T cells
Radiotherapy treatment within 4 weeks or less prior to veledimex dosing
Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
Known immunosuppressive disease, or autoimmune conditions, and/or chronic viral infections (eg, human immunodeficiency virus [HIV], hepatitis)
Use of systemic antibacterial, antifungal, or antiviral medications 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 allowed perioperatively.
Use of enzyme inducing antiepileptic drugs (EIAED) within 7 days prior to the first dose of study drug. Note: Levetiracetam (Keppra®) is not an EIAED and is allowed.
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 nonmetastatic prostate cancer
Nursing or pregnant females
Prior exposure to veledimex
Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex dosing without consultation with the Medical Monitor
Presence of any contraindication 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. Examples include, but are not limited to: unstable angina, congestive heart failure, myocardial infarction within 2 months of screening, ongoing maintenance therapy for life-threatening ventricular arrhythmia or uncontrolled asthma.
History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.