A Three-part, Phase I/II Dose-Escalation Study to Define the Safety, Tolerability, and Optimal Dose of Candidate GBM vaccine VBI-1901 with Subsequent Extension of Optimal Dose in Recurrent GBM subjects.
Objective
The purpose of this study is to assess the safety and tolerability of VBI-1901 in subjects with recurrent malignant gliomas (glioblastoma, or GBM).
Study Arms
- Experimental: Part A Dose Level 1
- Experimental: Part A Dose Level 2
- Experimental: Part A Dose Level 3
- Experimental: Part B GM-CSF Adjuvant
- Experimental: Part B AS01B Adjuvant
- Experimental: Part C VBI-1901 with GM-CSF Adjuvant
- Active Comparator: Part C Standard of Care Treatment
Eligibility
- 18-70 years of age
- Histologically confirmed WHO grade IV glioblastoma
- Unequivocal evidence of a tumor recurrence (any number of recurrences) or progression after an initial treatment regimen (prior to enrollment on this study) as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. An initial therapy requires surgery and radiation therapy, with or without temozolomide. In addition, alternate therapy (with or instead of temozolomide) is permitted as part of initial therapy.
- Recovery from the effects of surgery.
- Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days.
- Recovery from prior therapy toxicity defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia).
- Karnofsky performance status (KPS) score ≥ 70%.
- Adequate organ function, including the following:
- Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL
- Serum creatinine < 1.5 × the upper limit of normal (ULN)
- Bilirubin < 1.5 × ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN
- Women of childbearing potential: negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment.
- Female subjects of childbearing potential and sexually active male subjects must agree to use an acceptable form of contraception for heterosexual activity (i.e., oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for >30 days before Screening, during the study, and for 60 days after the last dose of study drug).
- Female subjects without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction.
- Able and willing to comply with protocol requirements in the opinion of the Investigator, including being able to have an MRI.
- Written consent has been obtained.
- Tumor specimen available for central pathological review.
