Chimeric Therapeutics Ltd (ASX:CHM) has successfully completed dosing of the first patient cohort in the phase 1 dose-escalation study to evaluate the safety and maximum tolerated dose of its Chlorotoxin CAR T (CLTX CAR T) treatment in patients with recurrent or progressive glioblastoma (GBM).
Dosing of the fourth patient marks the completion of planned dosing in the first and lowest dose level, with patients dosed via single site administration (intracranial intratumoral or intracavitary (ICT) administration) at a dose of 44 X 106 CLTX CAR T cells.
The study aims to enrol 18-36 patients with MMP2+ recurrent or progressive GBM across 4 dose levels.
Treatment targets tumours
CLTX CAR T uniquely utilises chlorotoxin (CLTX), a peptide derived from scorpion toxin, as the tumour-targeting component of the chimeric antigen receptor (CAR) which has been shown in preclinical models to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13.
In preclinical models, CLTX CAR T also demonstrated potent anti-tumour activity against glioblastoma while not exhibiting any off-tumour recognition of normal human cells/tissues, supporting a potentially optimal safety and efficacy profile.
Staggered dosing
As this is a first in human phase 1 cell therapy trial, the four patients dosed within this first cohort received staggered treatment, in accordance with FDA guidance.
Staggered treatment requires a follow-up interval between the administration of the product to one patient and administration of the product to the next patient, essentially only allowing for sequential treatment of patients with an interval long enough to monitor for adverse events between the dosing of each patient.
Patient recruitment
As the final patient of this first dose cohort successfully completes the DLT period, the study will begin to recruit patients for the next dose level which will introduce dual administration (ICT administration and intracranial intraventricular (ICV) administration) at a dose of 88 X 106 CAR T cells.
Beyond safety and efficacy, the study aims to establish the recommended dosing for a phase 2 trial.