BRiTE for Glioblastoma

(BRiTE Trial)

Overseen By Mustafa Khasraw, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mustafa Khasraw, MBChB, MD, FRCP, FRACP

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BRiTE for individuals with glioblastoma, a type of brain cancer. The primary goal is to determine if BRiTE (hEGFRvIII-CD3) is safe for patients with the EGFRvIII mutation. The trial seeks participants diagnosed with grade 4 malignant glioma who have completed radiation therapy. It aims to understand how different doses of BRiTE affect safety and may guide future treatments for this aggressive cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that hEGFRvIII-CD3 (BRiTE) is generally safe in both animal and human studies. In a study with mice, BRiTE did not cause any unusual health problems or major side effects, suggesting safety in animals.

In humans, studies have demonstrated that BRiTE can activate the immune system to target tumor cells, indicating it works as intended without unexpected issues.

Since this trial is in an early phase, the main goal is to assess safety. Researchers continue to gather information on how well people tolerate BRiTE. Reaching this stage indicates some confidence in its safety based on earlier research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about hEGFRvIII-CD3 (BRiTE) for glioblastoma because it targets a specific protein called EGFRvIII, which is often present in this aggressive brain cancer. Unlike standard treatments like surgery, radiation, and chemotherapy, which can affect both cancerous and healthy cells, BRiTE is designed to hone in on cancer cells expressing this unique protein, potentially leading to more effective and less toxic outcomes. Additionally, BRiTE's mechanism involves engaging the body's immune system to attack the cancer, offering a novel approach compared to traditional methods. This targeted action provides hope for improved treatment responses in patients with glioblastoma.

What evidence suggests that BRiTE might be an effective treatment for malignant glioma?

Studies have shown that the hEGFRvIII-CD3 (BRiTE) treatment, which participants in this trial will receive, may help patients with glioblastoma, a type of brain tumor. Research suggests that this treatment can boost the body's immune system to attack and destroy tumor cells. In animal studies, mice that received BRiTE treatment lived significantly longer than those that did not. While these results are encouraging, most evidence so far comes from animal studies, and more research is needed to confirm its effectiveness in humans. ^{2 3 5 6 7}

Who Is on the Research Team?

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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.

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

Known positive test for HIV

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Five escalating doses of continuously-infused BRiTE are planned: #1: 0.91 mcg/kg/day , #2: 2.88 mcg/kg/day, #3: 9.10 mcg/kg/day, #4: 28.78 mcg/kg/day, and #5: 91.00 mcg/kg/day.

Who Is Running the Clinical Trial?

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Lead Sponsor

Trials

4

Recruited

120+

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Adaptin Bio, Inc.

Collaborator

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12365897/

First-in-human study of an EGFRvIII x CD3 T cell bispecific ... Previous approaches targeting EGFR or EGFRvIII in newly diagnosed GBM have not demonstrated significantly improved outcomes for patients in clinical trials; ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6103776/

A Rationally Designed Fully Human EGFRvIII:CD3-Targeted ... These data demonstrate the hEGFRvIII-CD3 bi-scFv is able to mediate significant efficacy following intravenous administration in both subcutaneous and ...

3. withpower.com withpower.com/trial/phase-1-glioma-9-2021-3d904

BRiTE for Glioblastoma · Info for Participants In a phase II trial involving 49 patients with recurrent glioblastoma and EGFR amplification, dacomitinib showed limited efficacy, with a 6-month progression- ...

4. researchgate.net researchgate.net/publication/354731254_IMMU-05_A_PHASE_I_STUDY_IN_PROGRESS_OF_HEGFRVIII-CD3_BI-SCFV_BRITE_IN_PATIENTS_WITH_WHO_GRADE_IV_MALIGNANT_GLIOMA

immu-05. a phase i study in progress of hegfrviii-cd3 bi-scfv ... RESULTS Mice who received BRiTE and ALT demonstrated significantly enhanced survival compared to controls (median survival 29 vs 21 days, p=0.0135). Mice who ...

5. pnas.org pnas.org/doi/10.1073/pnas.1219817110

Systemic administration of a bispecific antibody targeting ... Treatment with i.v. bscEGFRvIIIxCD3 yielded extended survival in mice with well-established intracerebral tumors (P < 0.05) and achieved durable complete cure ...

6. academic.oup.com academic.oup.com/noa/article/3/Supplement_4/iv5/6372498

IMMU-05. A PHASE I STUDY IN PROGRESS OF HEGFRVIII ... We hypothesize that treatment of EGFRvIII-positive WHO grade IV malignant glioma with BRiTE alone or with peripheral T-cell infusion is safe and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12410358/

Comparative efficacy and safety of therapeutic strategies for ... Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, and EGFRvIII mutation has been associated with treatment ...