car t cells in patients with mmp2+ recurrent or progressive glioblastoma

Conditions: Glioblastoma Multiforme of Brain

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).

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).

Keywords: progressive or recurrent glioblastoma mmp2+