UPCC 06224 A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 (CDH17) Chimeric Antigen Receptor (CAR) T Cell Therapy for the Treatment of Relapsed or Refractory Gastrointestinal Cancers
Investigating Autologous CAR T-Cell Therapy for Advanced Gastrointestinal Cancers
Brief description of study
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.
Detailed description of study
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 of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Neuroendocrine Tumors, Colorectal Cancer, Gastric Cancer
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Age: 18 years - 85 years
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Gender: All
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Previous treatment with CDH17-targeted therapies.
- Unresolved toxicities from prior therapy except for chronic toxicity no greater than Grade 1 and stable > 30 days (Note: alopecia of any grade is not exclusionary).
- Uncontrolled seizure activity and/or known central nervous system (CNS) metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
- Uncontrolled Crohn's disease, ulcerative colitis, or other autoimmune or inflammatory disorders of the GI tract. "Uncontrolled" is defined as requiring hospitalization, corticosteroids, or chronic medication increase (dosage or frequency) within the previous 6 months.
- Liver involvement ≥ 50%.
- Active infection requiring oral or IV antibiotics.
- Current diagnosis of pleural effusions, interstitial lung disease, or heart failure of New York Heart Association Classification of Heart Failure Class III or IV.
- Ongoing treatment with systemic corticosteroid therapy at doses of prednisone ≥ 20 mg/day or equivalent (lower doses of corticosteroid therapy are allowed until 7 days prior to leukapheresis).
- No prior malignancy within 5 years except for non-melanomatous skin cancer or cervical cancer treated with curative intent
- Currently breastfeeding or planning to become pregnant within 9 months of study enrollment.
- Any other clinically significant uncontrolled illness or other comorbid condition that would, in the investigator's judgment, contraindicate the participant's participation in the clinical study.
This study investigates an investigational therapy using autologous CAR T-cells targeting Cadherin 17 (CDH17) for patients with advanced gastrointestinal cancers. These cancers have either returned after treatment or did not respond to standard treatments. The study aims to evaluate the safety and effectiveness of this therapy in patients with specific types of GI cancers, including gastric adenocarcinoma, colon and rectal adenocarcinoma, and certain neuroendocrine tumors.
Participants will undergo a procedure called leukapheresis to collect blood cells needed to create the CAR T-cell therapy. The process involves enriching T cells and modifying them to target cancer cells. Participants may receive chemotherapy between this procedure and the infusion of the CAR T-cells to keep their cancer stable. The study includes several phases, and participants will be monitored for up to 18 months or until their disease progresses.
- Who can participate: Adults aged 18 to 85 years with specific types of gastrointestinal cancers, such as gastric adenocarcinoma, colon, and rectal adenocarcinoma, may participate. They must have received prior cancer treatment and meet specific health criteria.
- Study details: Participants will provide consent and undergo screening for eligibility. They will have leukapheresis to collect cells for therapy manufacturing and may receive bridging chemotherapy while awaiting treatment.
- Study timelines: The study will last 18 months.
Study is selecting its participants from a population, or group of people, decided on by the researchers in advance.
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