Inclusion Criteria:
* Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on imaging studies
* Prior histopathology confirmed recurrent supratentorial WHO grade IV malignant glioma
* 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 female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal l 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 that do not contain estrogen (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.
* Age ≥ 18 years of age at the time of entry into the study
* Karnofsky Performance Score (KPS) ≥ 70%
* Hemoglobin ≥ 9 g/dl prior to biopsy
* 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 and catheter insertion, which can be attained with the help of platelet transfusion
* Neutrophil count ≥ 1000 cells/mm3 prior to biopsy
* Creatinine ≤ 1.5 x upper limit of normal (ULN) range prior to biopsy
* Total bilirubin ≤ 1.5 x ULN prior to biopsy, s (Exception: Patient has known Gilbert's Syndrome or patient has 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.)
* AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 2.5 x ULN prior to biopsy
* Prothrombin and Partial Thromboplastin Times ≤ 1.2 x ULN 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.
* At the time of biopsy, prior to administration of D2C7-IT, the presence of recurrent tumor must be confirmed by histopathological analysis
* A signed informed consent form approved by the Institutional Review Board (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
* Able to undergo brain MRI with and without contrast
Exclusion Criteria:
* Females who are pregnant or breast-feeding
* Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
* Patients with severe, active co-morbidity, defined as follow:
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 intercurrent 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 or uncontrolled diabetes mellitus
5. Patients with albumin allergy
6. Patients with severe (i.e., anaphylactic) gadolinium allergy. Patients with mild allergies (e.g., rash only) will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent
* Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks \[except for nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)\] prior to starting the study drug unless patients have recovered from side effects of such therapy. Patients should discontinue use of tumor- treating fields (TTFs), such as Optune™, at least one week prior to D2C7-IT infusion.
* Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy
* Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
* Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59 Gy)
1. If the MGMT promoter in their tumor is known to be unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial
2. If the MGMT promoter in their tumor is known to be methylated or the MGMT promoter methylation status is unknown at time of screening, patients must have received at least one chemotherapy regimen prior to participating in this trial
* 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); tumor crossing the midline or leptomeningeal disease
* Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion
* Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
* 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
* Patients with a known history of hypersensitivity to atezolizumab, or any components of atezolizumab
* Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
