Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma

NCT04547777 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00104852
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 study of an anti-CD40 monoclonal antibody (2141-V11) in combination with D2C7-IT for patients with recurrent World Health Organization (WHO) grade III or IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Conditions

Glioma, Malignant

Keywords

D2C7; D2C7-IT; Glioblastoma; Glioma; 2141-V11; Pro00104852; Duke; Rockefeller; CD40; epidermal growth factor receptor (EGFR); EGFR; Landi

Outcome Measures

Primary Outcomes (3)

• Proportion of patients with dose-limiting toxicity (DLT) within each dose level

  DLTs are defined as any of the following events that are at least possibly, probably, or definitely attributable to study treatment (2141-V11 or the combination of D2C7-IT and 2141-V11) during dose escalation. As the optimal dose of D2C7-IT in monotherapy has been well established, only toxicity starting or increasing in grade at any time after the start of 2141-V11 will be considered for DLT definition.

  28 days after catheter removal

• Proportion of patients with unacceptable toxicity resulting from injections of 2141-V11 in the CPL area ipsilateral to the tumor

  For the purpose of monitoring adverse events occurring with perilymphatic injections of 2141-V11, we will define an unacceptable toxicity as any adverse event that satisfies the definition of DLT.

  28 days after catheter removal

• The proportion of patients with Tumor Monorail Device (TMD)-related unacceptable adverse event

  Unacceptable adverse events following TMD placement are defined as follows * Cerebral edema (grade 3 or higher) due to device implantation * New neurological symptoms (grade 3 or higher) that do not resolve within 2 weeks and not due to tumor progression * Device-related infection (grade 3 or higher) * Intracranial hemorrhage (grade 3 or higher) * Tumor mis-migration (extracranial extension)

  14 days following TMD placement

Study Arms (2)

D2C7-IT + 2141-V11

EXPERIMENTAL

Single D2C7-IT intratumoral infusion (4613.2 ng/mL in 36 mL) over 72 hours followed by single 2141-V11 (3.0 mg, RP2D established prior to V5.0) infusion (5 dose levels) over 7 hours. This will be followed 2 weeks later by initiation of CPL subcutaneous injections of 2141-V11 at 2.0 mg, which will be repeated again 2 weeks later and then every 3 weeks for 1 year.

Drug: D2C7-IT; Drug: 2141-V11

D2C7-IT + 2141-V11 and Tumor Monorail Device (TMD) Placement

EXPERIMENTAL

Patients who meet eligibility and agree with TMD placement will have the TMD implanted approximately 14 days prior to D2C7-IT infusion. Intraoperative CT will be performed post implant to ensure device location accuracy and check for hemorrhage. Prior to catheter insertion for D2C7-IT infusion, the first tumor/fluid sampling through the TMD will occur. Repeated tumor/fluid sampling via the TMD will occur prior to every 2141-V11 perilymphatic infusion, i.e., approximately 2 weeks (+ 1 week) after D2C7-IT and then every 3 weeks for 1 year.

Drug: D2C7-IT; Drug: 2141-V11

Interventions

D2C7-IT DRUG

D2C7-IT intratumoral infusion

D2C7-IT + 2141-V11; D2C7-IT + 2141-V11 and Tumor Monorail Device (TMD) Placement

2141-V11 DRUG

2141-11 intratumoral infusion

Also known as: anti-CD40

D2C7-IT + 2141-V11; D2C7-IT + 2141-V11 and Tumor Monorail Device (TMD) Placement

Eligibility Criteria

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

You may qualify if:

• Study population:
• Subgroup #2: Histopathologically confirmed recurrent supratentorial WHO grade 3 or 4 malignant glioma (high grade glioma with molecular features of glioblastoma will be eligible under WHO grade 4 malignant glioma)
• Subgroup #3: Histopathologically confirmed recurrent supratentorial WHO grade 4 malignant glioma (high grade glioma with molecular features of glioblastoma will be eligible under WHO grade 4 malignant glioma) and found amenable for Tumor Monorail Device (TMD) implantation as per the treating neurosurgeon
• Patient or partner(s) meets one of the following criteria:
• Non-childbearing potential (i.e.) not sexually active, physiologically incapable of becoming pregnant, including people who are post-menopausal or surgically sterile. Surgically sterile people are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation or have had a vasectomy. 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 (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 prior to biopsy
• Creatinine ≤ 1.5 x normal range prior to biopsy
• Total bilirubin ≤ 1.5 x ULN prior to biopsy (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.)
• AST/ALT ≤ 2.5 x ULN
• Prothrombin and Partial Thromboplastin Times ≤ 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.

You may not qualify if:

• Patients who are pregnant or breastfeeding/chestfeeding
• 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 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 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 have received treatment with tumor treating fields (e.g., Optune) ≤ 1 week prior to starting the study drug
• 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 (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.)
• 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
• Rockefeller University: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Related Publications (1)

• Parker S, McDowall C, Sanchez-Perez L, Osorio C, Duncker PC, Briley A, Swartz AM, Herndon JE 2nd, Yu YA, McLendon RE, Tedder TF, Desjardins A, Ashley DM, Gunn MD, Enterline DS, Knorr DA, Pastan IH, Nair SK, Bigner DD, Chandramohan V. Immunotoxin-alphaCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. Sci Transl Med. 2023 Feb 8;15(682):eabn5649. doi: 10.1126/scitranslmed.abn5649. Epub 2023 Feb 8.

  PMID: 36753564 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Health

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

D2C7-(scdsFv)-PE38KDEL

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

• Annick Desjardins, MD,FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Annick Desjardins, MD. FRCPC

CONTACT

919-684-5301; dukebrain1@dm.duke.edu

Stevie Threatt

CONTACT

919-684-5301; dukebrain1@dm.duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• 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: September 8, 2020
• First Posted: September 14, 2020
• Study Start: July 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)