A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy
18 - 85 Years, Male and Female
CHM-2101-001 (primary)
NCI-2024-07692
Summary
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.
Objectives
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.
Eligibility
- Documented informed consent of the participant and/or legally authorized representative.
- Confirmed histologic diagnosis of one of the following solid tumors of GI origin:
- Gastric adenocarcinoma Note: for gastric adenocarcinoma patients only, central laboratory confirmation of CDH17+ tumor expression is required.
- Colon and/or rectal adenocarcinoma
- G1, G2, and well-differentiated G3 neuroendocrine tumors of the midgut and hindgut (ileal, jejunal, cecal, distal colonic, or rectal; with = 55% Ki67 expression)
- Availability of unstained tumor tissue slides from archived tumor tissue or a new tumor biopsy, if medically feasible. Note: for gastric adenocarcinoma patients only, confirmation of CDH17+ is required prior to study inclusion.
- Have received at least 1 prior line of systemic anti-cancer treatment in the locally advanced or metastatic setting, as defined by National Comprehensive Cancer Network (NCCN) guidelines. Participants must have received or declined FDA-approved and available treatment options, including targeted therapies for disease mutation or antigen expression status.
- Age = 18 years and = 85 years.
- For Phase 1 Dose Expansion and Phase 2 only: Measurable disease as per RECIST v1.1 criteria (Note: Measurable disease is NOT required for Phase 1 Dose Escalation).
- Eastern Cooperative Oncology Group (ECOG) = 1.
- Life expectancy = 12 weeks.
- No known contraindications to leukapheresis, cyclophosphamide, fludarabine, or steroids.
- Baseline laboratory values as shown in the following table: Minimum Laboratory Values for Study Entry Laboratory Assessment Criteria White blood cell count > 4,000/mm3 Absolute neutrophil count (ANC) = 1,500/mm3 Platelets = 100,000/mm3 Hemoglobin = 10 g/dL Total bilirubin = 1.5 x upper limit of normal (ULN) Aspartate amino transferase (AST) = 3 x ULN Alanine transaminase (ALT) = 3 x ULN Creatinine clearance by Cockroft-Gault equation 60 mL/min Oxygen saturation = 92% on room air Albumin = 3 g/dL
- Left ventricular ejection fraction = 50%.
- 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 (WOCBP) 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 through at least 3 months after the last dose of CHM-2101.
Treatment Sites in Georgia
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