This is a treatment clinical trial to assess the efficacy of ERC1671 in combination with bevacizumab and pembrolizumab in patients with GBM that has progressed following treatment with radiation and temozolomide.

Patients will have surgery to collect the maximum amount of GBM tissue that can be reasonably collected. This tissue will be used to manufacturer ERC1671 for the patient.

The patients will receive ERC1671 in combination with GM-CSF and cyclophosphamide, in combination with bevacizumab and pembrolizumab.

The treatment cycles will be 28 days long and follow the schedule below. There are 28 days (± 7 days) from surgery date to start of Cycle 1 day 1 to permit production of ERC-D vaccine:

The treatment will be repeated every 28-days until progression of disease, intolerance, or a decision by the physician and/or patient to withdraw from the treatment plan.

Efficacy will be evaluated as a foundation of Overall Survival reported at twelve months (OS12)

Safety will be evaluated, as a secondary objective, throughout the trial by the incidence of serious adverse events (AEs), physical examination findings, vital signs and clinical laboratory test results. SAEs will be graded for severity using NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.

Patients will undergo brain MRI as part of standard care before starting cycle 1 and every 8 weeks thereafter (+/- 7 days) until disease progression, and whenever progression is suspected based on clinical symptoms. Tumor response will be assessed using both the Macdonald and the iRANO response criteria for high-grade gliomas, which considers radiologic imaging, neurological status, and steroid dosing.

Whenever clinically appropriate, stereotactic biopsy or resection will be performed in accordance with standard of care for patients with progressive disease. To differentiate true progression from potentially toxic or therapeutic inflammatory responses presenting as radiographic or clinical changes, histologic verification of progression will be performed whenever feasible and appropriate.

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO grade IV malignant gliomas (glioblastoma) and meet the following inclusion criteria:
• Age ≥18 years of age.
• KPS of ≥ 60%.
• Life expectancy > 12 weeks.
• First, second, third or fourth relapse of glioblastoma.
• Previous treatment for glioblastoma must include surgery (biopsy, partial resection, or full surgical resection), conventional radiation therapy and temozolomide (TMZ).
• MRI record must be obtained showing the MRI was done at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy, or at least 4 weeks after radiation for a new lesion outside the prior primary radiation field unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are two MRIs confirming progressive disease that are 8 weeks apart.
• If prior therapy with gamma knife or other focal high-dose radiation, must have subsequent histologic documentation of local relapse, or relapse with new lesion outside the irradiated field.
• Resolution of all chemotherapy or radiation-related toxicities ≤ CTCAE Grade severity, except for alopecia and hematologic toxicity. Patients taking temozolomide can start study treatment 23 days from the last temozolomide dose. For all other chemotherapy drugs, study treatment can start as long as all adverse events related to their prior treatment are no higher than Grade 1.
• Systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day 1.
• Bi-dimensionally measurable disease (as per iRANO criteria).
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin (Hbg) > 9g/dL,
• Leukocytes >1,500/mcL
• Absolute neutrophil count>1,000/mcL
• CD4 count > 300/mcl
• Platelets >125,000/mcL
• Serum bilirubin = 1.5 × upper limit of normal (ULN) or = 3 x ULN if Gilbert's disease is documented AST(SGOT) and ALT(SGPT)<2.5 x institutional upper limit of normal
• Serum creatinine < 1.5 mg/dl
• Signed informed consent approved by the Institutional Review Board;
• If sexually active, patients must agree to take contraceptive measures for the duration of the treatments.

Exclusion Criteria:

• Subjects unable to undergo an MRI with contrast
• Subjects able and willing to participate in an open and accruing ERC clinical trial
• Presence of diffuse leptomeningeal disease
• History, presence, or suspicion of metastatic disease
• Administration of immunosuppressive drugs less than 2 weeks prior to first dose of ERC1671 except dexamethasone for cerebral edema as detailed above;
• Known contraindication or hypersensitivity to any component of bevacizumab.
• Evidence of recent hemorrhage on screening MRI of the brain with the following exceptions: presence of hemosiderin; resolving hemorrhagic changes related to surgery; presence of punctate hemorrhage in the tumor.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1.
• Evidence of bleeding diathesis or coagulopathy as documented by an elevated PT, PTT or bleeding time and clinically significant;
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 1.
• Urine protein: creatinine ratio 1.0 at screening;
• Anticipation of need for major surgical procedure during the course of the study.
• Serious non-healing wound, ulcer, or bone fracture.
• Active infection requiring treatment, known immunosuppressive disease, active systemic autoimmune diseases such as lupus, receipt of systemic immunosuppressive therapy, human immunodeficiency virus (HIV) infection, Hepatitis B or Hepatitis C.
• Uncontrolled hypertension, blood pressure of > 150 mmHg systolic and > 100 mmHg diastolic, or history of hypertensive encephalopathy. Subjects with any known uncontrolled inter-current illness including ongoing or active infection, symptomatic congestive heart failure (NYHA Gr.2 or >), myocardial infarction, unstable angina pectoris within the past 12 months
• Stroke, transient ischemic attack, unstable angina, myocardial infarction or congestive heart failure (New York Heart Association Grade II or greater) within the past 12 months. Unstable or severe intercurrent medical conditions, chronic renal disease, or uncontrolled diabetes mellitus.
• Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test prior to Day 1 and agree to use reliable contraception whilst study participant.
• Men refusing to exercise a reliable form of contraception.
• History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with Prostate Surface Antigen (PSA) level \