BRiTE for Glioblastoma

(BRiTE Trial)

Overseen By Mustafa Khasraw, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Duke University

Must be taking: Temozolomide

Must not be taking: Corticosteroids

Disqualifiers: Pregnancy, CNS bleeding, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids at a dose of 2 mg dexamethasone daily or more, you must stop them at least 14 days before the first BRiTE injection.

What data supports the effectiveness of the BRiTE treatment for glioblastoma?

Research shows that the BRiTE treatment, which uses a special antibody to guide immune cells to attack glioblastoma cells with a specific mutation (EGFRvIII), has been effective in reducing tumor size and extending survival in animal models. This suggests it could be a promising approach for treating glioblastoma in humans. ^{1 2 3 4 5}

Is hEGFRvIII-CD3 (BRiTE) safe for humans?

In a study with mice, the treatment hEGFRvIII-CD3 (BRiTE) did not show any abnormal clinical signs or significant toxic effects. Some minor changes in blood and urine tests were noted, but no harmful effects were observed. ^{3 6 7 8 9}

What makes the BRiTE treatment unique for glioblastoma?

The BRiTE treatment is unique because it targets the EGFRvIII mutation, a common driver in glioblastoma, by potentially disrupting the EGFRwt-EGFRvIII-HB-EGF loop that maintains tumor growth, offering a novel approach compared to standard therapies that do not specifically address this mutation. ^{1 4 5 8 10}

What is the purpose of this trial?

This trial is testing a new treatment called BRiTE for patients with aggressive brain cancer that have a specific mutation. BRiTE helps the immune system recognize and destroy cancer cells by connecting immune cells directly to the cancer.

Research Team

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Principal Investigator

Duke University

Eligibility Criteria

Adults with Grade IV malignant glioma and EGFRvIII mutation, who've completed standard radiation therapy. Eligible if KPS is ≥70%, liver function is adequate, not pregnant or breastfeeding, no recent severe infections or unresolved toxicities from previous treatments (except stable conditions like hair loss), and willing to use effective birth control.

Inclusion Criteria

Total bilirubin ≤ 2 x upper limit of normal (exceptions apply for Gilbert's Syndrome)

Creatinine ≤ 1.2 x normal range

Hemoglobin ≥ 9.0 g/dL

Exclusion Criteria

My side effects from previous cancer treatments are mild.

Known positive test for HIV

I have been taking 2 mg or more of dexamethasone daily for the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a bolus BRiTE injection followed by a 28-day safety monitoring period

4 weeks

1 visit (in-person) for injection, multiple visits for monitoring

Follow-up

Participants are passively followed as part of their standard of care follow-up

7 weeks

Treatment Details

Interventions

• hEGFRvIII-CD3 (BRiTE)

Trial Overview The trial tests a new cancer treatment called BRiTE for patients with specific brain tumors. It's in phase 1 to check safety. Patients must have the EGFRvIII mutation and meet certain health criteria to join.

Participant Groups

Group I: hEGFRvIII-CD3 (BRiTE) infusion Experimental Treatment 1 Intervention

Four escalating doses of BRiTE are planned: #1: 57.0 ng/kg, #2: 570.0 ng/kg, #3: 5700.0 ng/kg, and #4: 57000.0 ng/kg.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Findings from Research

EGFRvIII, a mutant form of the epidermal growth factor receptor, is a key driver of glioblastoma (GBM) and relies on PDGFRA signaling for tumor growth, highlighting a potential therapeutic target.

In patient-derived xenograft models, effective anti-tumor treatment requires simultaneous inhibition of both EGFRvIII and PDGFRA, suggesting that targeting these pathways together could improve treatment outcomes for GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. Yeo, AT., Jun, HJ., Appleman, VA., et al.[2023]

In a phase II trial involving 49 patients with recurrent glioblastoma and EGFR amplification, dacomitinib showed limited efficacy, with a 6-month progression-free survival rate of only 10.6%.

The treatment was associated with significant adverse effects, as 40.8% of patients experienced grade 3-4 drug-related side effects, primarily diarrhea and rash, highlighting the need for careful patient selection based on molecular characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Sepúlveda-Sánchez, JM., Vaz, MÁ., Balañá, C., et al.[2022]

References

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

An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of EGFRvIII. [2021]

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

A Rationally Designed Fully Human EGFRvIII:CD3-Targeted Bispecific Antibody Redirects Human T Cells to Treat Patient-derived Intracerebral Malignant Glioma. [2023]

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

A Novel EGFRvIII T-Cell Bispecific Antibody for the Treatment of Glioblastoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

EGFRvIII-mediated transactivation of receptor tyrosine kinases in glioma: mechanism and therapeutic implications. [2021]

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

GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody. [2020]

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

Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. [2022]

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

EGFR-AKT-Smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction. [2018]

10. England pubmed.ncbi.nlm.nih.gov

A minority subpopulation of CD133(+) /EGFRvIII(+) /EGFR(-) cells acquires stemness and contributes to gefitinib resistance. [2021]