D2C7-IT + 2141-V11 Combination Post-resection in RGBM

Inclusion Criteria:

1. Age ≥ 18 years old at the time of entry into the study

2. Histopathologically confirmed WHO grade 4 IDHwt GBM (high grade glioma withmolecular features of glioblastoma will be eligible)

3. Karnofsky Performance Score (KPS) ≥ 70%

4. Hemoglobin ≥ 9 g/dl prior to biopsy

5. Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study;however, because of risks of intracranial hemorrhage with catheter placement,platelet count ≥ 125,000/µl is required for the patient to undergo biopsy andcatheter insertion, which can be attained with the help of platelet transfusion.

6. Neutrophil count ≥ 1000 prior to biopsy

7. Creatinine ≤ 1.5 x normal range prior to biopsy

8. Total bilirubin ≤ 1.5 x ULN prior to biopsy (Exception: Participant has known orsuspected Gilbert's Syndrome for which additional lab testing of direct and/orindirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)

9. AST/ALT ≤ 2.5 x ULN

10. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.Patients with prior history of thrombosis/embolism are allowed to be onanticoagulation, understanding that anticoagulation will be held in theperioperative period per the neurosurgical team's recommendations. Low molecularweight heparin (LMWH) is preferred. If a patient is on warfarin, the internationalnormalized ratio (INR) is to be obtained and value should be below 2.0 prior tosurgical resection and biopsy.

11. Patient must have undergone resection per the recommendation of their treatingphysician 3-5 weeks prior to administration of D2C7-IT, and the presence ofrecurrent tumor must have been confirmed by histopathological analysis.

12. Able to undergo brain MRI with and without contrast a. Post-surgery MRI must demonstrate a residual area of non-enhancing disease thatis amenable to CED infusion (no larger than 3 x 3 cm of residual enhancing diseaseper screening MRI)

13. Patient or partner(s) meets one of the following criteria:

14. Non-childbearing potential (i.e. not sexually active, physiologically incapableof becoming pregnant, including any female who is post-menopausal or surgicallysterile, or any male who has had a vasectomy). Surgically sterile females aredefined as those with a documented hysterectomy and/or bilateral oophorectomyor tubal ligation. Postmenopausal for purposes of this study is defined as 1year without menses.; or

15. Childbearing potential and agrees to use one of the following methods of birthcontrol: approved hormonal contraceptives (e.g. birth control pills, patches,implants, or infusions), an intrauterine device, or a barrier method ofcontraception (e.g. a condom or diaphragm) used with spermicide.

16. A signed ICF approved by the IRB will be required for patient enrollment into thestudy. Patients must be able to read and understand the ICF and must sign the ICFindicating that they are aware of the investigational nature of this study

Exclusion Criteria:

1. Females who are pregnant (negative pregnancy test at screening visit) or breast-feeding

2. Patients with an impending, life-threatening cerebral herniation syndrome, based onthe assessment of the study neurosurgeons or their designate

3. Patients with severe, active co-morbidity, defined as follow:

4. Patients with an active infection requiring intravenous treatment or having anunexplained febrile illness (Tmax > 99.5°F/37.5°C)

5. Patients with known immunosuppressive disease or known human immunodeficiencyvirus infection

6. Patients with unstable or severe intercurrent medical conditions such as severeheart disease (New York Heart Association Class 3 or 4)

7. Patients with known lung (forced expiratory volume in the first second ofexpiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus

8. Patients with albumin allergy

9. Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except fornitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide orcyclophosphamide (1 week)] prior to starting the study drug unless patients haverecovered from side effects of such therapy

10. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the studydrug unless patients have recovered from side effects of such therapy

11. Patients may not have received treatment with tumor treating fields (e.g., Optune®)

• 1 week prior to starting the study drug

7. Patients may not be less than 12 weeks from radiation therapy, unless progressivedisease outside of the radiation field or 2 progressive scans at least 4 weeks apartor histopathologic confirmation

8. Patients who have not completed all standard of care treatments, including surgicalprocedure and radiation therapy (Please note: For patients under 65 years old,standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks.For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15 fractions over 3 weeks.)

9. If the MGMT promoter in their tumor is known to be unmethylated, patients arenot mandated to have received chemotherapy prior to participating in this trial

10. If the MGMT promoter in their tumor is known to be methylated or the MGMTpromoter methylation status is unknown at time of screening, patients must havereceived at least one chemotherapy regimen prior to participating in this trial

11. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord;radiological evidence of active (growing) disease (active multifocal disease);extensive subependymal disease (tumor touching subependymal space is allowed); tumorcrossing the midline or leptomeningeal disease

12. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior tothe D2C7-IT infusion

13. Patients with worsening steroid myopathy (history of gradual progression ofbilateral proximal muscle weakness, and atrophy of proximal muscle groups)

14. Patients with prior, unrelated malignancy requiring current active treatment withthe exception of cervical carcinoma in situ and adequately treated basal cell orsquamous cell carcinoma of the skin

15. Patients with active autoimmune disease requiring systemic immunomodulatorytreatment within the past 3 months

16. Patients who cannot undergo MRI due to obesity or to having certain metal in theirbodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses,joints, rods, or plates)