BRiTE - Bispecific T Cell Engager for Patients With Glioblastoma

NCT04903795 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00108079
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1 study will assess the safety of a novel brain Bispecific T cell engager (BRiTE) in patients with newly diagnosed or recurrent World Health Organization (WHO) Grade 4 glioblastoma (GBM). Owing to its short half-life, the study drug, BRiTE, will be continuously infused intravenously (IV) for 4 days (96 hours) in a 28-day cycle. Given that BRiTE specifically exerts its effects on tumor cells expressing the Epidermal Growth Factor Receptor variant III (EGFRvIII) mutation, we will only enroll patients with EGFRvIII-positive tumors in this study. The primary objective is to evaluate the safety and tolerability of continually infused BRiTE in ndGBM and rGBM patients and determine the maximum tolerated dose (MTD) for continuously infused BRiTE.

Conditions

Newly Diagnosed Glioblastoma; Recurrent Glioblastoma

Keywords

EGFRvIII; Khasraw; BRiTE; Pro00108079

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT)

  Proportion of patients with DLT within each dose level

  Begins with the infusion of BRiTE during Cycle 1 and goes through 28 days from the time of initiation of the infusion

Secondary Outcomes (2)

• Objective response rate (ORR)

  8 weeks

• Pharmacokinetic (PK) of BRiTE observed during Cycle 1 of BRiTE infusion

  Prior to initiation of Cycle 1 (each cycle is 28 days) of BRiTE infusion (baseline; on Day 0) till 1 hour after the end of infusion (on Day 4)

Study Arms (1)

hEGFRvIII-CD3 (BRiTE) infusion

EXPERIMENTAL

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.

Drug: hEGFRvIII-CD3 (BRiTE)

Interventions

hEGFRvIII-CD3 (BRiTE) DRUG

Bispecific T cell engager possessing one effector binding arm specific for the epsilon subunit of CD3 (a signaling molecule complex associated with the T cell receptor on T cells) while the opposing target-binding arm is directed against the hEGFRvIII epitope that is differentially expressed on the surface of tumor cells

Also known as: BRiTE

hEGFRvIII-CD3 (BRiTE) infusion

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
• For both newly diagnosed and recurrent patients, pathologically documented supratentorial WHO grade 4 GBM with a confirmed EGFRvIII mutation at the most recent diagnosis, with radiographic contrast enhancing disease that is ≤ 4 cm in maximal diameter in any plane before resection.
• i. ndGBM patients: Must have undergone surgical resection of their tumor. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria. Newly diagnosed patients must complete standard of care RT with or without TMZ before participation, depending on the MGMT promoter methylation status as follows:
• Patients with methylated MGMT promoter status should have received standard of care concomitant RT and TMZ, followed by 6 cycles of adjuvant TMZ, before they can participate in this study
• Patients with an unmethylated MGMT promoter status should have received standard of care RT, but need not have received concomitant TMZ or 6 cycles of adjuvant TMZ and can be enrolled after 4 weeks from completion of standard of care RT
• Patients whose MGMT status is unknown or indeterminate will be treated as though they have a methylated MGMT promotor status for eligibility purposes
• RT for 3 or 6-week courses are accepted as follows:
• Typically, 59.4-60 Gy over approximately 6 weeks duration, if under 65 years old
• A minimum of 40 Gy over 3 weeks duration, if 65 years or older
• Patients who progress during RT or within 4 weeks after completion of RT are not eligible.
• ii. rGBM patients at first progression: Must have pathological or radiographic confirmation of their tumor recurrence that is ≤ 4 cm in maximal diameter in any plane.
• Note: Patients that undergo total gross resection at time of recurrence are eligible to enroll. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria.
• Karnofsky Performance Score (KPS) ≥ 70%
• Hematological function as follows:
• i. Hemoglobin ≥ 9.0 g/dL ii. Absolute neutrophil count (ANC) ≥ 750/mm3 iii. Platelet count ≥ 50,000

You may not qualify if:

• Patients who are pregnant or breastfeeding/chestfeeding
• Patients with baseline corrected QT interval (QTc) \> 480ms on screening electrocardiogram (ECG).
• Note: QTc measurements will use Fridericia's correction method (QTcF).
• Known hypersensitivity to immunoglobulins or to any other component of BRiTE
• Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
• Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Patients with severe, active co-morbidity, defined as follows:
• i. Patients with an active infection requiring IV treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C) ii. Patients with known immunosuppressive disease or known HIV infection, with CD4+ T cell counts \< 350 cells/µl iii. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4) iv. Patients with known lung (forced expiratory volume in the first second of expiration \[FEV1\] \< 50%) disease or uncontrolled diabetes mellitus v. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
• Patients with known Human Immunodeficiency Virus (HIV) positive status only if CD4+ T cell counts \< 350 cells/µl. Patients with known HIV and CD4+ T cell counts over 350 cells/µl are eligible.
• Patients with known hepatitis C virus (HCV) positive status, who have not completed curative antiviral treatment and have HCV viral load above the limit of quantification. Patients with well-controlled HCV are eligible.
• Patients with known hepatitis B virus (HBV) infection, with evidence of a hepatitis B surface antigen, indicative of an active infection. Patients with well-controlled HBV are eligible.
• Patients on corticosteroids ≥ 2 mg dexamethasone daily or equivalent within 7 days of 1st BRiTE infusion
• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
• Patients who previously received other therapeutic interventions for ndGBM, with the exception of surgical resection and standard of care concomitant RT and TMZ (including adjuvant TMZ) for their brain tumor
• Patients who have had only a biopsy prior to receiving standard of care concomitant RT and TMZ

Sponsors & Collaborators

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP: lead
• Adaptin Bio: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Health

MeSH Terms

Conditions

Glioblastoma

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

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

CONTACT

9196845301; dukebrain1@dm.duke.edu

Stevie Threatt, BA

CONTACT

9196845301; 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: May 19, 2021
• First Posted: May 27, 2021
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)