VB-111 in Surgically Accessible Recurrent/Progressive GBM

Inclusion Criteria: ° ± µ ™ ® * Histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). * First or second progression of glioblastoma/gliosarcoma (according to RANO criteria) following standard of care treatment upon initial diagnosis with radiation. * Measurable disease by RANO criteria at progression. * The maximal tumor volume at baseline meets the following criteria as determined by a local site investigator or surgeon: Longest diameter ≤ 4CM. * Surgically resectable disease at progression. * An interval of the following durations prior to randomization: * At least 28 days from prior surgical resection, or 7 days from stereotactic biopsy * At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression * At least 23 days from prior chemotherapy * At least 42 days from nitrosureas * At least 42 days from other anti-tumor therapies (including vaccines) * At least 28 days from any investigational agent NOTE: no wash-out period required from TTF. * Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide. * Corticosteroid use at or less than dexamethasone 2mg daily. Participants should be on a stable or decreasing dose for at least 7 days prior to randomization. * Age ≥ 18 years on day of signing informed consent * KPS ≥ 70% (see Appendix A) * Adequate bone marrow, liver, and renal function according to the following criteria: * Absolute neutrophil count ≥ 1,500 cells/mL \~ 1.5 K/μL * Platelets ≥ 100,000 cells/mL \~ 100 K/μL * Total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤ institutional ULN for subjects with total bilirubin levels \> 1.5 institutional ULN * Aspartate aminotransferase (AST) ≤ 2.0 x ULN * Serum creatinine level ≤ ULN or creatinine clearance ≥ 50 mL/min for participants with creatinine levels above normal limits (calculated by the Cockcroft-Gault formula) * Ability to understand and willingness to sign a written informed consent document * Availability of 10 unstained formalin-fixed paraffin-embedded slides. * MRI within 14 days prior to registration. * NOTE: Due to the fact that the screening MRI will not be used for response purpose, participants may be registered if screening CT or MRI is \> 14 days of registration if prospective approval is received from Overall PI * Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin urine or serum pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * NOTE: Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 20 pg/mL or have had surgical bilateral oophorectomy (withor without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of child bearing potential. * Males and females of childbearing potential must utilize a standard contraception method throughout the trial and up to 120 days after the last dose of treatment on study. * NOTE: Women of childbearing potential and men with female spouses of childbearing potential must agree to use two methods of reliable contraception simultaneously or to practice complete abstinence from heterosexual contact prior to study entry, while receiving treatment, and for 4 months after undergoing treatment. One method must include a highly effective method such as an intrauterine device, hormonal (birth control pills, injections or implants), tubal ligation or partner's vasectomy. The other method can be an additional hormonal therapy or barrier method such as a male condom, diaphragm or cervical cap. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately Exclusion Criteria: * Current or planned participation in a study of an investigational agent or using an investigational device. * Has tumor primarily localized to the brainstem or spinal cord * Has presence of diffuse leptomeningeal disease or extracranial disease. * Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment * Minor surgical procedure (e.g. stereotactic biopsy or shunt placement) within 7 days of first study treatment, placement of vascular access within 2 days of first study treatment * Expected to have surgery other than the neurosurgical procedure intended for the GBM lesion during study treatment period * Prior stereotactic radiotherapy (Note: those who have had biopsy proven tumor recurrence at a site of SRS treatment should be considered eligible if approved by the study central Investigator) * Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.) * Prior administration of the study drug VB-111 * Concomitant medication that may interfere with study results (e.g. immunosuppressive agents other than inhaled, topical or intra-articular steroids or a stable or decreasing dose of oral corticosteroids of up to \<2 mg/day dexamethasone equivalent) * Known active second malignancy. Exceptions include non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Participants are not considered to have currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening * Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * History of stroke or transient ischemic attack within 6 months prior to randomization * Evidence of CNS hemorrhage CTCAE grade 2 or above on screening MRI * Active cardiac disease within 6 months prior to randomization (i.e. acute coronary syndrome, unstable angina, New York Heart Association grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment) * Significant vascular disease within 6 months prior to randomization (e.g. aortic aneurysm requiring surgical repair, peripheral arterial thrombosis, symptomatic peripheral vascular disease) * History of venous thromboembolism CTCAE version 5.0 grade 3 or greater * Known proliferative and/or vascular retinopathy * Inadequately controlled hypertension (defined as systolic blood pressure \> 150mmHg and/or diastolic blood pressure \> 100mmHg) within 1 week of randomization * History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 6 months of randomization. * History of active gastrointestinal bleeding within 6 months prior to randomization. * History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation) * Current or recent (within 10 days of study randomization) use of aspirin \> 325mg/day, clopidogrel \> 75mg/day or equivalent. Therapeutic or prophylactic use of anticoagulants is allowed * Known liver disease (alcoholic, drug/toxin induced, genetic or autoimmune) * History of gastrointestinal perforation or abscess * Positive testing to any of the following viruses: HIV, HBV, HCV within the last 6 months. Exceptions include participants with serology positive for HBV indicating past exposure but without evidence of active infection (e.g. negative PCR) * History of intracranial abscess within 6 months prior to randomization * Serious non-healing wound, active ulcer, or untreated bone fracture * Pregnant or breastfeeding participants