• 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.

• 18-70 years of age.

• Histologically confirmed WHO grade IV glioblastoma.

• Unequivocal evidence of a first tumor recurrence with measurable disease, of an area no greater than 400 mm2, which may include patients with resected first recurrence tumor after an initial treatment regimen (prior to enrollment on this study) consisting of surgical intervention (tumor resection) and radiation, with or without temozolomide chemotherapy (depending on the MGMT methylation status), as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. In addition, alternate chemotherapy (with or instead of temozolomide) is permitted as part of initial therapy.

• At least 12 weeks since radiotherapy treatment and/or 23 days after chemotherapy prior to first dose of VBI-1901.

• 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; absolute lymphocyte count ≥ 500/uL;

‣ 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 must have a 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.

⁃ Written consent has been obtained.

⁃ Tumor specimen available for central pathological review.

• 18 years of age or older (no age upper limit).

• Histologically confirmed supratentorial 2016 WHO classification grade IV Glioblastoma, IDH-wildtype or grade 4 in the 2021 WHO classification. Tumors that are histologically lower grade but are classified as glioblastoma using the WHO 2021 criteria because of molecular alterations (TERT promoter mutation and/or EGFR amplification and/or combined chromosome 7 gain/10 loss) are not eligible.

• Unequivocal evidence of a first tumor recurrence with measurable disease of an area no greater than 600 mm2, which may include patients with resected first recurrence tumor, after an initial treatment regimen (prior to enrollment on this study) consisting of surgical intervention (tumor resection) and radiation, with or without temozolomide chemotherapy (depending on the MGMT methylation status), as assessed by MRI of the brain with and without contrast completed within 30 days prior to screening visit, if not it should be performed as part of screening visit. In addition, alternate bio/chemotherapy (with or instead of temozolomide) other than nitrosourea is permitted as part of initial therapy.

• At least 12 weeks since radiotherapy treatment and/or 23 days after chemotherapy prior to first dose of VBI-1901 or SOC treatment. Patients with recurrent GBM within 12 weeks of radiation therapy may be included if they have surgically proven tumor recurrence (i.e.

• this is proven to not be pseudoprogression).

• Recovery from the effects of surgery.

• Corticosteroid (dexamethasone or equivalent) dosage ≤ 2 mg daily that has been stable for at least 5 days before randomization into the study.

• 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; Absolute lymphocyte count ≥ 500/uL; CD4/CD8 ratio ≥1 or CD4 count ≥ 400/uL;

‣ 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 must have a negative urine pregnancy test within 21 days prior to the start of 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 \> 40 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.

⁃ Written consent has been obtained.