The goal of this clinical trial is to evaluate CHM-2101, an autologous CDH17 CAR T-cell therapy for the treatment of advanced gastrointestinal (GI) cancers that are relapsed or refractory to at least 1 standard treatment regimen in the metastatic or locally advanced setting.
This is a Phase 1/2 open-label study to evaluate CHM-2101, an autologous CDH17 CAR T-cell therapy for the treatment of advanced gastrointestinal (GI) cancers that are relapsed or refractory to at least 1 standard treatment regimen in the metastatic or locally advanced setting. The study has 2 parts: Phase 1, Dose Escalation and Expansion, and Phase 2. Potential participants will provide written consent and be screened for study eligibility prior to undergoing any screening procedures, including leukapheresis. Protocol-specified criteria must be met prior to the start of leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). Eligible participants will undergo leukapheresis to collect PBMCs for product manufacturing, which comprises enrichment of T cells, lentiviral transduction, ex vivo expansion, and cryopreservation of the CHM-2101 cell product. Participants who have a leukapheresis or manufacturing failure may be permitted a second attempt at leukapheresis. Bridging chemotherapy (treatment between the time of leukapheresis and first dose of lymphodepleting chemotherapy \[LDC\]) is permitted at the discretion of the investigator, if needed to maintain disease stability during CHM-2101 manufacturing time. Bridging chemotherapy is prohibited within the 2 weeks prior to leukapheresis and 2 weeks prior to planned CHM-2101 infusion. Specific criteria to proceed should be reviewed prior to leukapheresis, LDC, and CHM-2101 infusion. Participants will be followed in this study for 18 months or until disease progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
135
Cadherin 17 (CDH17) Chimeric Antigen Receptor (CAR)-positive T cells
Emory University
Atlanta, Georgia, United States
RECRUITINGUniversity of Chicago
Chicago, Illinois, United States
RECRUITINGUniversity of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGDose-Limiting Toxicity (DLT)
Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Time frame: 28 Days
Rates and Grades of Cytokine Release Syndrome (CRS)
Assessed per American Society for Transplant and Cellular Therapy (ASTCT) consensus grading guideline
Time frame: up to 15 years
All other adverse events and toxicities
Assessed per NCI CTCAE v5.0
Time frame: up to 15 years
Objective Response Rate (ORR)
Assessed by RECIST v 1.1
Time frame: up to 15 years
Disease control rate (DCR)
Assessed as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response, and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Time frame: up to 15 years
Time to response (TTR)
Measured as the amount of time elapsed until drug response is achieved for the first time.
Time frame: up to 15 years
Duration of response (DOR)
Measured as the amount of time a patient responds to a treatment before disease progresses or the patient dies.
Time frame: up to 15 years
Progression-free survival (PFS)
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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Sarah Cannon Research Institute
Nashville, Tennessee, United States
RECRUITINGTime frame: up to 15 years
Overall survival (OS)
Measured from the date of first infusion of CAR-T cells until death.
Time frame: up to 15 years