HEGFRvIII-CD3 (BRiTE)

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

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.

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.

Live record on ClinicalTrials.gov →

• 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

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.