50 Participants Needed

D2C7-IT + 2141-V11 for Glioblastoma

ST
Daniel Landi, MD profile photo
Overseen ByDaniel Landi, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Darell Bigner
Must be taking: Temozolomide
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11 in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adults newly diagnosed with a type of cancerous brain tumor called glioblastoma. The word "investigational" means the study drugs are still being tested in research studies and are not approved by the U.S. Food and Drug Administration (FDA).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anticoagulation therapy, it may be held during the perioperative period (around the time of surgery) as per the neurosurgical team's recommendations.

Is the D2C7-IT + 2141-V11 treatment generally safe for humans?

Preclinical studies in mice and rats have shown promising results for the safety of D2C7-IT and Fc-engineered anti-CD40 antibodies, with toxicity being manageable when delivered directly into tumors. Early human trials are underway to further evaluate safety, but results are not yet conclusive.12345

What makes the D2C7-IT + 2141-V11 treatment unique for glioblastoma?

The D2C7-IT + 2141-V11 treatment is unique because it combines a targeted immunotoxin that attacks specific proteins on glioblastoma cells with an engineered antibody that stimulates the immune system, potentially overcoming the tumor's ability to suppress immune responses. This approach aims to enhance the body's natural defenses against the tumor, offering a novel strategy compared to traditional treatments like surgery, radiation, and chemotherapy.13456

What data supports the effectiveness of the treatment D2C7-IT + 2141-V11 for glioblastoma?

Research shows that the combination of D2C7-IT and an anti-CD40 antibody can activate the immune system and lead to long-term tumor-specific immune responses in glioblastoma models, resulting in cures in mice. This suggests potential effectiveness in treating glioblastoma by enhancing the body's immune response against the tumor.178910

Who Is on the Research Team?

Daniel Landi, MD | Neuro-oncologist ...

Daniel Landi, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed glioblastoma, a type of brain tumor, who've had surgery to remove it but still have some remaining disease. They must be in good health otherwise, with proper organ function and blood counts, not on high doses of steroids or anticoagulants that can't be paused for surgery. Participants should not be pregnant or breastfeeding and must agree to use birth control if they can have children.

Inclusion Criteria

Total bilirubin ≤ 1.5 x ULN prior to catheter placement
I have a specific type of brain tumor (glioblastoma) that has been surgically removed but still shows signs on scans.
My platelet count is high enough for tests and procedures.
See 9 more

Exclusion Criteria

I do not have severe health issues that could interfere with the treatment.
I am not pregnant or breastfeeding.
I am at risk of a severe brain condition due to pressure increase.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intratumoral Infusion

Single infusion of D2C7-IT over 3 days followed by a single infusion of 2141-V11 over 7 hours delivered to the tumor margins through a catheter placed in the brain

3 days

Subcutaneous Injection and Radiation

First subcutaneous injection of 2141-V11 around the lymph nodes of the head and neck, followed by standard radiation therapy lasting 3 to 6 weeks

3-6 weeks

Post-Radiation Injections

Resumption of 2141-V11 injections around the lymph nodes of the head and neck, starting 1 week after radiation and continuing every 3 weeks for up to a year

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • 2141-V11
  • D2C7-IT
Trial Overview The trial is testing two investigational drugs: D2C7-IT given once inside the brain after surgery and 2141-V11 injected multiple times under the skin near lymph nodes. The study aims to see how safe these treatments are and how well they work against glioblastoma when combined with standard radiation therapy.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: D2C7-IT + 2141-V11Experimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Darell Bigner

Lead Sponsor

Trials
8
Recruited
380+

Rockefeller University

Collaborator

Trials
162
Recruited
16,700+

Published Research Related to This Trial

The combination of D2C7-immunotoxin (IT) and αCD40 costimulation significantly enhances anti-tumor immunity in glioblastoma models, leading to long-term tumor-specific CD8+ T cell responses and even cures in mice.
This promising preclinical success has led to the initiation of a phase 1 clinical trial (NCT04547777) to evaluate the safety and efficacy of the D2C7-IT+αhCD40 treatment in human patients with malignant glioma.
Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.Parker, S., McDowall, C., Sanchez-Perez, L., et al.[2023]
Higher levels of CD40/CD40L expression in grade III gliomas are associated with better prognoses in patients with glioblastoma, suggesting it could serve as a useful biomarker for treatment outcomes.
The use of FGK45, an agonistic antibody targeting CD40, in combination with OX86 significantly prolonged survival in glioma models, indicating a promising immunotherapeutic strategy for treating gliomas.
CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models.Chonan, M., Saito, R., Shoji, T., et al.[2018]
Systemic delivery of αCD40 antibodies in preclinical glioma models leads to the formation of tertiary lymphoid structures (TLS), which are associated with increased T cell infiltration in treatment-naïve glioma patients.
Despite promoting TLS formation, αCD40 treatment results in hypofunctional T cells and impairs the effectiveness of immune checkpoint inhibitors, likely due to the accumulation of suppressive CD11b+ B cells in the tumor microenvironment.
Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma.van Hooren, L., Vaccaro, A., Ramachandran, M., et al.[2021]

Citations

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. [2023]
CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models. [2018]
Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma. [2021]
Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor beta. [2023]
Inhibitory IgG Receptor-Expressing Cells: The Must-Have Accessory for Anti-CD40 Immunomodulatory mAb Efficacy. [2018]
A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma. [2022]
Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. [2023]
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. [2019]
EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Fc-engineered anti-CD40 antibody enhances multiple effector functions and exhibits potent in vitro and in vivo antitumor activity against hematologic malignancies. [2021]
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