D2C7-IT With Atezolizumab for Recurrent Gliomas

NCT04160494 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: Pro00101898FOR0003
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 study of atezolizumab in combination with D2C7-IT, a dual-specific monoclonal antibody (mAB) with a high affinity for both EGFRwt- and EGFRvIII-expressing cells, in patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Conditions

Malignant Glioma

Keywords

D2C7; D2C7-IT; Atezolizumab; Randazzo; Glioblastoma; Glioma; Bigner; Pro00101898; Genentech; CTEP; Duke; Landi

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with an unacceptable adverse event

  An unacceptable adverse event includes any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, any life-threatening event, or any treatment-related death. Also included are any grade 2 or higher serious autoimmune toxicities, particularly those affecting vital organs (e.g. cardiac, renal, CNS) if it occurs within 2 weeks of any protocol treatment.

  2 years

Study Arms (2)

D2C7-IT (6920 ng/mL) + Atezolizumab

EXPERIMENTAL

Single D2C7-IT convection-enhanced delivery (CED) infusion (6920 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years

Drug: D2C7-IT (6920 ng/mL via convection-enhanced delivery); Drug: Atezolizumab (1200 mg every three weeks)

D2C7-IT (4613.2 ng/mL) + Atezolizumab

EXPERIMENTAL

Single D2C7-IT convection-enhanced delivery (CED) infusion (4613.2 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years

Drug: Atezolizumab (1200 mg every three weeks); Drug: D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)

Interventions

D2C7-IT (6920 ng/mL via convection-enhanced delivery) DRUG

dual-specific mAB

D2C7-IT (6920 ng/mL) + Atezolizumab

Atezolizumab (1200 mg every three weeks) DRUG

programmed cell death ligand 1 (PD-L1) blocking antibody

Also known as: Tecentriq

D2C7-IT (4613.2 ng/mL) + Atezolizumab; D2C7-IT (6920 ng/mL) + Atezolizumab

D2C7-IT (4613.2 ng/mL via convection-enhanced delivery) DRUG

dual-specific mAB

D2C7-IT (4613.2 ng/mL) + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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,
• 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

You may not qualify if:

• 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:
• Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
• Patients with known immunosuppressive disease or known human immunodeficiency virus infection
• Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
• Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) \< 50%) disease or uncontrolled diabetes mellitus
• Patients with albumin allergy
• 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)
• 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
• 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

Sponsors & Collaborators

• Darell Bigner: lead
• Istari Oncology, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Health

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

D2C7-(scdsFv)-PE38KDEL; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Study Officials

• Daniel Landi, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: E. L. and Lucille F. Jones Cancer Distinguished Research Professor, in the School of Medicine

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 13, 2019
• Study Start: February 25, 2020
• Primary Completion: June 28, 2024
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)