Ignite Creation Date:
2025-12-24 @ 2:10 PM
Ignite Modification Date:
2026-01-01 @ 7:56 AM
Study NCT ID:
NCT04903795
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-11-03
First Post:
2021-05-19
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
BRiTE - Bispecific T Cell Engager for Patients With Glioblastoma
Sponsor:
Mustafa Khasraw, MBChB, MD, FRCP, FRACP
Organization:
Study Overview
Official Title:
A Phase 1 Study of Bispecific T Cell Engager (BRiTE) in Patients With Newly Diagnosed or Recurrent Glioblastoma
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BRiTE
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.
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.
Detailed Description:
This proposed Phase 1 study will treat a maximum of 18 patients with pathologically documented supratentorial EGFRvIII-positive ndGBM or rGBM.
ndGBM patients: Participants with ndGBM must have undergone surgical resection of their tumor and completed standard of care RT with or without TMZ, depending on the status of O-6 methylguanine DNA methyltransferase (MGMT) promoter methylation as indicated below:
1\) ndGBM patients with a methylated MGMT promoter should have received standard of care concomitant RT and TMZ, followed by 6 cycles of adjuvant TMZ, before they can participate in this study 2) ndGBM patients with an unmethylated MGMT promoter should have received standard of care RT, but need not have received concomitant TMZ or 6 cycles of adjuvant TMZ and can be enrolled 4 weeks after completion of standard of care RT 3) RT for 3 or 6-week courses are accepted as follows: i. Typically, 59.4-60 Gy over approximately 6 weeks duration, for patients under 65 years old ii. A minimum of 40 Gy over 3 weeks duration, for patients 65 years or older. Note: Patients who progress during RT or within 4 weeks after completion of RT are not eligible to participate in this study.
rGBM patients at first progression: Participants with rGBM can enroll if they have pathological or radiographic confirmation of their tumor recurrence. Patients that undergo total gross resection at time of recurrence are eligible to enroll.
Once deemed eligible upon screening, patients will receive a continuous IV infusion of BRiTE for 4 days (96 hours), followed by 24 days off-treatment, for a total period of 28 days. This 28-day period is 'Cycle 1'. Patients may continue receiving BRiTE infusions for 2 subsequent 'maintenance' cycles, each lasting for 28 days (Cycles 2 and 3): continuous BRiTE infusion for 4 days (96 hours), followed by 24 days off-treatment. Cohorts of 3 patients will be treated with increasing levels of continuously infused BRiTE in Cycle 1 to determine the MTD of BRiTE. Patients will be monitored for dose-limiting toxicity (DLT) during the DLT observation period that lasts for 28 days from the time of initiation of BRiTE infusion during Cycle 1. Patients will also be monitored for safety during the subsequent maintenance cycles of BRiTE. Along with safety, this study will include both preliminary assessments of clinical benefit and PK analysis of BRiTE.
ndGBM patients: Participants with ndGBM must have undergone surgical resection of their tumor and completed standard of care RT with or without TMZ, depending on the status of O-6 methylguanine DNA methyltransferase (MGMT) promoter methylation as indicated below:
1\) ndGBM patients with a methylated MGMT promoter should have received standard of care concomitant RT and TMZ, followed by 6 cycles of adjuvant TMZ, before they can participate in this study 2) ndGBM patients with an unmethylated MGMT promoter should have received standard of care RT, but need not have received concomitant TMZ or 6 cycles of adjuvant TMZ and can be enrolled 4 weeks after completion of standard of care RT 3) RT for 3 or 6-week courses are accepted as follows: i. Typically, 59.4-60 Gy over approximately 6 weeks duration, for patients under 65 years old ii. A minimum of 40 Gy over 3 weeks duration, for patients 65 years or older. Note: Patients who progress during RT or within 4 weeks after completion of RT are not eligible to participate in this study.
rGBM patients at first progression: Participants with rGBM can enroll if they have pathological or radiographic confirmation of their tumor recurrence. Patients that undergo total gross resection at time of recurrence are eligible to enroll.
Once deemed eligible upon screening, patients will receive a continuous IV infusion of BRiTE for 4 days (96 hours), followed by 24 days off-treatment, for a total period of 28 days. This 28-day period is 'Cycle 1'. Patients may continue receiving BRiTE infusions for 2 subsequent 'maintenance' cycles, each lasting for 28 days (Cycles 2 and 3): continuous BRiTE infusion for 4 days (96 hours), followed by 24 days off-treatment. Cohorts of 3 patients will be treated with increasing levels of continuously infused BRiTE in Cycle 1 to determine the MTD of BRiTE. Patients will be monitored for dose-limiting toxicity (DLT) during the DLT observation period that lasts for 28 days from the time of initiation of BRiTE infusion during Cycle 1. Patients will also be monitored for safety during the subsequent maintenance cycles of BRiTE. Along with safety, this study will include both preliminary assessments of clinical benefit and PK analysis of BRiTE.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: