CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma

NCT05627323 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CHM-1101-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Glioblastoma Multiforme of Brain

Keywords

Progressive or recurrent glioblastoma; MMP2+

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT)

  Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

  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).

  up tp 15 years

• All other adverse events and toxicities

  Assessed per NCI CTCAE v5.0.

  up to 15 years

Secondary Outcomes (7)

• Chimeric antigen receptor (CAR) T cell

  up to 15 years

• Endogenous T cell

  up to15 years

• Human anti-CAR antibody (HACA)

  up to 15 years

• Progression free survival (PFS) time

  12 months

• Overall survival (OS)

  up to 15 years

Study Arms (2)

Treatment (CAR T cell therapy) 1

EXPERIMENTAL

Arm 1 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle. Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations. After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

Biological: CHM-1101 CAR-T cells

Treatment (CAR T cell therapy) 2

EXPERIMENTAL

Arm 2 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle. Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations. After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

Biological: CHM-1101 CAR-T cells

Interventions

CHM-1101 CAR-T cells BIOLOGICAL

Administered via ICT/ICV dual delivery

Also known as: Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT/ICV dual delivery), Chlorotoxin-CD28-CD3z-CD19t-expressing CAR T-cells

Treatment (CAR T cell therapy) 1; Treatment (CAR T cell therapy) 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the subject and/or legally authorized representative.
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
• Age 18 years and older.
• ECOG status of 0 or 1.
• Life expectancy ≥12 weeks.
• Subject has a prior histologically confirmed diagnosis of a grade 4 glioblastoma multiforme (GBM) or a prior histologically confirmed diagnosis of a grade 2 or 3 malignant glioma and now has radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or has a unifocal relapse of GBM.
• Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy and ≥ 12 weeks after completion of front-line radiation therapy.
• Confirmed MMP2+ tumor expression by IHC (≥20% moderate/high MMP2 score \[2+ or 3+\]).
• Adequate venous access to perform leukapheresis.
• No known contraindications to leukapheresis or steroids.
• In-range baseline laboratory values for WBC (\>2000/dL \[or ANC ≥1000/mm\^3\]), platelets (≥75000/mm\^3), total bilirubin (≤1.5xULN), AST (≤2.5xULN), ALT (≤2.5xULN), serum creatinine (≤1.5xmg/dL), and oxygen saturation (≥95% on room air)
• Seronegative for human immunodeficiency virus (HIV) by antigen/antibody (Ag/Ab) testing.
• Seronegative for hepatitis B and/or hepatitis C virus.
• Women of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
• Agreement by women AND men of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CHM-1101. (Childbearing potential is defined as not being surgically sterilized (women and men) or, for women, having not been free from menses for \> 1 year.)

You may not qualify if:

• Within 3 months of having received prior bevacizumab therapy at the time of enrollment.
• Not yet recovered from toxicities of prior therapy.
• Uncontrolled seizure activity and/or clinically evident progressive encephalopathy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Clinically significant uncontrolled illness.
• Active infection requiring antibiotics.
• Known history of HIV or hepatitis B or hepatitis C infection.
• Other active malignancy.
• Women only-pregnant or breastfeeding.
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
• Prospective subjects who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Sponsors & Collaborators

• Chimeric Therapeutics: lead

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

St. David's South Austin Medical Center - Sarah Cannon - Austin

Austin, Texas, 78704, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Chlorotoxin

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two dose levels investigated, with both dose levels proceeding in parallel. Expansion or de-escalation decision rules are based on a traditional 3+3 clinical study design.

Study Record Dates

• First Submitted: November 16, 2022
• First Posted: November 25, 2022
• Study Start: June 6, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2041
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)