This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).
This is a phase 1b, multicenter, feasibility/safety study of the dual delivery (administered through both intracavitary/intratumoral \[ICT\] and intraventricular \[ICV\] catheters) of CHM-1101, an autologous chlorotoxin-chimeric antigen receptor (CLTX-CAR) cell product, in participants with recurrent or progressive GBM. The investigational product is identified as CHM-1101 (CLTX(EQ)28ζ/CD19t+ CAR T cells). PRIMARY OBJECTIVE • To determine the recommended phase 2 dose (RP2D) for dual ICT and ICV delivery of CHM-1101 in participants with MMP2+ recurrent or progressive GBM. SECONDARY OBJECTIVES * To assess the feasibility and safety of dual delivery of CHM-1101. * To describe the persistence, expansion, immunogenicity, and phenotype of CHM-1101 and endogenous cells tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF). * In participants who receive at least 2 of the 3 planned doses of CHM-1101 in Cycle 1: * Estimate the progression-free survival (PFS) rates * Estimate the overall survival (OS) rates * To evaluate the disease response rate.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Administered via ICT/ICV dual delivery
City of Hope Medical Center
Duarte, California, United States
St. David's South Austin Medical Center - Sarah Cannon - Austin
Austin, Texas, United States
Dose-limiting toxicity (DLT)
Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Time frame: 28 days
Cytokine Release Syndrome (CRS)
Assessed per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading guideline, evaluating levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry).
Time frame: up tp 15 years
All other adverse events and toxicities
Assessed per NCI CTCAE v5.0.
Time frame: up to 15 years
Chimeric antigen receptor (CAR) T cell
Assess levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry).
Time frame: up to 15 years
Endogenous T cell
Assess level and phenotype detected in TCF, PB, and CSF (absolute number per µL by flowcytometry).
Time frame: up to15 years
Human anti-CAR antibody (HACA)
Serum samples will be evaluated for HACA against the CLTX(EQ)28ζ therapeutic agent.
Time frame: up to 15 years
Progression free survival (PFS) time
Measured from the date of first infusion of CAR-T cells until the first date when progressive disease (PD) is objectively documented or death from any cause, whichever is earlier.
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Time frame: 12 months
Overall survival (OS)
Measured from the date of first infusion of CAR-T cells until death.
Time frame: up to 15 years
Disease response
Assessed by modified Response Assessment in Neuro-Oncology Criteria (RANO) criteria.
Time frame: 12 months
Clinical benefit rate
The proportion of participants who experience a complete response, a partial response, or stable disease that is 3 months or greater in duration.
Time frame: 12 months