D2C7-IT for Brain Cancer

Overseen By Stevie Threatt

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Darell Bigner

Must not be taking: Immunotherapeutics, Antiangiogenics, Alkylating agents

Disqualifiers: Pregnancy, Unstable systemic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 72 hours

81 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like immunotherapeutic agents, antiangiogenic agents, and some chemotherapies must be stopped a few weeks before enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment D2C7-IT for brain cancer?

Research shows that D2C7-IT, a treatment targeting specific proteins in brain tumors, has been effective in killing cancer cells in lab tests and animal studies. It has shown promise in improving survival rates in mice with brain tumors, and early results from human trials are encouraging. ^{1 2 3 4 5}

Is D2C7-IT safe for humans?

In preclinical studies on rats, D2C7-IT showed some safety concerns at high doses, such as weight loss and abnormal behavior, but no major issues at lower doses. The maximum safe dose was determined to guide human trials, which are ongoing. ^{1 2 3 4 5}

How is the D2C7-IT drug different from other brain cancer treatments?

D2C7-IT is unique because it specifically targets two proteins, EGFRwt and EGFRvIII, that are often overexpressed in glioblastomas, and it is delivered directly into the brain tumor using a method called convection-enhanced delivery. This approach not only kills tumor cells but also stimulates the immune system to help fight the cancer. ^{1 2 3 4 6}

What is the purpose of this trial?

This trial is testing a new medicine called D2C7-IT for patients with aggressive brain tumors that have returned. The medicine is delivered directly into the tumor to ensure it spreads evenly and targets cancer cells. The goal is to find the safest and most effective dose for future studies.

Research Team

Dan Landi, MD

Principal Investigator

Preston Robert Tisch Brain Tumor Center at Duke University Medical Center

Eligibility Criteria

Adults over 18 with recurrent high-grade brain tumors (WHO grade III or IV malignant glioma) who've had prior treatment, can undergo MRI scans, and agree to use contraception. They must have good performance status and adequate organ function. Excluded are those with certain medical conditions, recent treatments, or severe allergies.

Inclusion Criteria

You have a type of brain tumor called grade III or IV malignant glioma that has come back after treatment.

You have been diagnosed with a high-grade malignant brain tumor in the top part of the brain.

Before getting the treatment, a biopsy must confirm that the tumor has come back.

Exclusion Criteria

You have a serious brain condition that needs urgent treatment.

You have been taking more than 4mg of dexamethasone per day in the 2 weeks before starting the treatment.

You have received certain types of chemotherapy within a specific time period before enrolling in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive D2C7-IT administered intratumorally via convection-enhanced delivery following confirmatory diagnostic biopsy

72 hours

Continuous hospital stay

Initial Follow-up

Participants are evaluated for adverse events and monitored for safety

2 weeks

1 visit (in-person)

Extended Follow-up

Participants are monitored every 8 weeks for safety and effectiveness until 48 weeks

48 weeks

6 visits (in-person)

Treatment Details

Interventions

• D2C7-IT

Trial Overview The trial is testing D2C7-IT delivered directly into the tumor in the brain to find the safest dose for future studies. Patients will receive a biopsy followed by catheter placement for infusion if recurrent glioma is confirmed.

Participant Groups

Group I: D2C7-IT Experimental Treatment 1 Intervention

Recurrent malignant glioma patients will receive D2C7-IT, delivered intratumorally by CED following confirmatory diagnostic biopsy.

Who Is Running the Clinical Trial?

Darell Bigner

Lead Sponsor

Trials

8

Recruited

380+

Findings from Research

D2C7-IT, an immunotoxin targeting specific EGFR proteins, demonstrated significant tumor-killing ability in glioblastoma cells, with effective in vitro IC50 values of 0.47 ng/mL and 1.05 ng/mL for CT-2A and SMA560 cells, respectively.

Combining D2C7-IT with immune checkpoint inhibitors (αCTLA-4 and αPD-1) not only prolonged survival in murine models of glioma but also led to complete tumor regressions in some cases, indicating a promising strategy for enhancing antitumor immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. Chandramohan, V., Bao, X., Yu, X., et al.[2023]

A novel tumor-targeted immunotoxin, D2C7-IT, has been developed to specifically target and kill glioblastoma cells expressing the EGFRwt and EGFRvIII proteins, showing effective cytotoxicity in various glioblastoma cell lines and xenograft models.

D2C7-IT has demonstrated robust anti-tumor efficacy in mouse models and has passed preclinical toxicity studies, leading to FDA approval for a Phase I/II clinical trial, indicating its potential as a new treatment option for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. Bao, X., Pastan, I., Bigner, DD., et al.[2020]

The novel immunotoxin D2C7-(scdsFv)-PE38KDEL effectively targets both the wild-type epidermal growth factor receptor (EGFR) and the EGFR deletion mutant (EGFRvIII), which are commonly found in glioblastoma.

This immunotoxin has shown strong anti-cancer effects in established murine glioma models, indicating its potential as a therapeutic option for treating this aggressive brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma. Chandramohan, V., Bigner, DD.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. [2023]