Clinical trial NCT05627323: CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma
Official title: A Phase 1b Study to Evaluate CHM-1101, a CAR T-Cell Therapy With a Chlorotoxin Tumor-Targeting Domain for Patients With Matrix Metallopeptidase 2 Positive (MMP2+) Recurrent or Progressive Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioblastoma Multiforme of Brain
Keywords: Progressive or recurrent glioblastoma
MMP2+
Lead sponsor: Chimeric Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-11-25
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.)

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 28 days
measure: Cytokine Release Syndrome (CRS)
timeFrame: up tp 15 years
measure: All other adverse events and toxicities
timeFrame: up to 15 years
Secondary outcomes:
measure: Chimeric antigen receptor (CAR) T cell
timeFrame: up to 15 years
measure: Endogenous T cell
timeFrame: up to15 years
measure: Human anti-CAR antibody (HACA)
timeFrame: up to 15 years
measure: Progression free survival (PFS) time
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: up to 15 years
measure: Disease response
timeFrame: 12 months
measure: Clinical benefit rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Austin
country: United States
facility: St. David's South Austin Medical Center - Sarah Cannon - Austin
state: Texas
Study officials:
affiliation: Chimeric Therapeutics
name: Jason Litten, MD
role: STUDY_DIRECTOR
References: