IND application withdrawn

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.

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).