D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients

Inclusion Criteria: 1. Age ≥ 18 years of age at the time of entry into the study 2. Newly diagnosed supratentorial GBM, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of GBM will be eligible under WHO 4 malignant glioma) with residual radiographic non-contrast enhancing disease on the post-2 cycles of adjuvant TMZ MRI amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane. 3. Patient must have completed standard of care radiation therapy (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older) in combination with TMZ and 2 cycles of post-radiation, adjuvant TMZ. For patients known to be MGMT promoter unmethylated prior to start of radiation therapy, patients are not mandated to have received TMZ in combination to radiation therapy prior to participating in this trial. 4. Karnofsky Performance Score (KPS) \> 70% 5. Able to undergo brain MRI wiht and without contrast 6. Hemoglobin ≥ 9 g/dl prior to catheter placement 7. Platelet count ≥ 100,000/µL unsupported. Because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion 8. Neutrophil count ≥ 1000 prior to catheter placement 9. Creatinine ≤ 1.5 x normal range prior to catheter placement 10. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) prior to catheter placement (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.) 11. AST/ALT ≤ 2.5 x ULN 12. PT and PTT ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to biopsy. 13. Patient or partner(s) meets one of the following criteria: 1. Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any person who is post-menopausal or surgically sterile, or any person who has had a vasectomy). Surgically sterile people are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or 2. Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide 14. A signed ICF approved by the IRB will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study Exclusion Criteria: 1. Patients who are pregnant or breast-feeding/chestfeeding 2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate 3. Patients with severe, active comorbidity, defined as follows: 1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C) 2. Patients with known immunosuppressive disease or known human immunodeficiency virus infection 3. Patients with unstable or severe medical conditions such as severe heart disease (New York Heart Association Class 3 or 4) 4. Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) \< 50%) disease 5. Patients with uncontrolled diabetes mellitus 6. Patients with albumin allergy 7. Patients with known HIV or Hepatitis C positive status 8. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy 4. Patients who previously received other therapeutic interventions for newly diagnosed GBM with the exception of surgical resection and standard of care concomitant radiation therapy and TMZ and 2 cycles of post-radiation, adjuvant TMZ for their brain tumor 5. Patients who have received concomitant radiation therapy and TMZ ≤ 11 weeks prior to start of D2C7-IT CED infusion 6. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of (actively growing) multifocal disease, tumor crossing the midline, extensive subependymal disease, or leptomeningeal disease 7. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the start of D2C7-IT infusion 8. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups) 9. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin 10. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months 11. Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates) or patients with any known severe allergies to contrast agents. Patients with mild allergies (i.e., rash only) are allowed to enroll and will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent.