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

NCT06455605 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00115800
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and efficacy of the combination of D2C7-IT+2141-V11 administered in the non-enhancing tumor of patients with resected recurrent glioblastoma (rGBM) via convection enhanced delivery (CED), followed by subcutaneous cervical perilymphatic injections (CPLIs) of 2141-V11 2 and 4 weeks post infusion, then every 3 weeks for a year, and every 4-6 weeks thereafter if patients benefit from therapy.

Conditions

Recurrent Glioblastoma IDH Wildtype

Keywords

D2C7; D2C7-IT; 2141-V11; Pro00115800; GBM; Glioblastoma; convection-enhanced delivery; CED; IDHwt

Outcome Measures

Primary Outcomes (2)

• Primary Outcome - Safety

  Describe the safety of the combination of D2C7-IT+2141-V11 administered in non-enhancing tumor of recurrent GBM patients via CED, followed by cervical perilymphatic subcutaneous injections of 2141-V11. The proportion of patients who experience unacceptable toxicity will be reported.

  5 years

• Primary Outcome - Efficacy

  To assess overall survival defined as the time between initiation of treatment with D2C7-IT+2141-V11 and death or last follow-up if alive. Median overall survival will be reported

  6 years

Study Arms (1)

D2C7-IT + 2141-V11

EXPERIMENTAL

Single D2C7-IT intratumoral infusion (4613.2 ng/mL in 36 mL) over 72 hours followed by an 2141-V11 infusion over 7 hours. This is followed by injections of 2141-V11 (2mg) in the cervical perilymphatic (CPLI) subcutaneous area ipsilateral to the tumor at weeks 2, 4, 7, 10 and then every 3 weeks until week 49. After week 49 (equivalent of 1 year of every 3 weeks CPLI of 2141-V11), patients who have completed 1 year of CPL subcutaneous injections of 2141-V11 at 2 mg every 3 weeks, who benefit from the therapy, and desire to continue on therapy, will receive CPLI of 2141-V11 at 2 mg every 4-6 weeks.

Drug: D2C7-IT; Drug: 2141 V11

Interventions

D2C7-IT DRUG

D2C7-IT will be dosed at 166,075 ng in 36 mL.

D2C7-IT + 2141-V11

2141 V11 DRUG

2141-V11 will be dosed at 3 mg in 3.5 mL for CED administration. 2141-V11 in the cervical perilymphatic subcutaneous area will be dosed at 2 mg.

D2C7-IT + 2141-V11

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old at the time of entry into the study
• Histopathologically confirmed WHO grade 4 IDHwt GBM (high grade glioma with molecular features of glioblastoma will be eligible)
• 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 surgical resection and biopsy.
• Patient must have undergone resection per the recommendation of their treating physician 3-5 weeks prior to administration of D2C7-IT, and the presence of recurrent tumor must have been confirmed by histopathological analysis.
• Able to undergo brain MRI with and without contrast
• a. Post-surgery MRI must demonstrate a residual area of non-enhancing disease that is amenable to CED infusion (no larger than 3 x 3 cm of residual enhancing disease per screening MRI)
• 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 ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or

You may not qualify if:

• Females who are pregnant (negative pregnancy test at screening visit) 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 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®)
• 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

Sponsors & Collaborators

• Darell Bigner: lead
• Rockefeller University: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Health Clinical Trials

MeSH Terms

Conditions

Glioblastoma

Interventions

D2C7-(scdsFv)-PE38KDEL

Condition Hierarchy (Ancestors)

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

Study Officials

• Annick Desjardins, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Annick Desjardins, MD

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 12, 2024
• Study Start: March 17, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)