A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy

NCT06055439 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CHM-2101-001
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Neuroendocrine Tumors; Colorectal Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (4)

• Dose-Limiting Toxicity (DLT)

  Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

  28 Days

• Rates and Grades of Cytokine Release Syndrome (CRS)

  Assessed per American Society for Transplant and Cellular Therapy (ASTCT) consensus grading guideline

  up to 15 years

• All other adverse events and toxicities

  Assessed per NCI CTCAE v5.0

  up to 15 years

• Objective Response Rate (ORR)

  Assessed by RECIST v 1.1

  up to 15 years

Secondary Outcomes (5)

• Disease control rate (DCR)

  up to 15 years

• Time to response (TTR)

  up to 15 years

• Duration of response (DOR)

  up to 15 years

• Progression-free survival (PFS)

  up to 15 years

• Overall survival (OS)

  up to 15 years

Study Arms (1)

Autologous CDH17 CAR T-cell Therapy

EXPERIMENTAL

After receiving three daily doses of IV fludarabine and cyclophosphamide, participants will receive a single dose of IV CHM-2101. The dose of CHM-2101 during Phase 1 will be based on "3+3" rules of dose escalation. The recommended Phase 2 dose will be based on results from the Phase 1.

Biological: CHM-2101 CAR-T cells

Interventions

CHM-2101 CAR-T cells BIOLOGICAL

Cadherin 17 (CDH17) Chimeric Antigen Receptor (CAR)-positive T cells

Autologous CDH17 CAR T-cell Therapy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• Previous treatment with CDH17-targeted therapies.
• 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.

Sponsors & Collaborators

• Chimeric Therapeutics: lead

Study Sites (4)

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors; Colorectal Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Officials

• Jennifer Eads, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chimeric Clinical

CONTACT

(323) 366-9009; clinical@chimerictherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 26, 2023
• Study Start: May 15, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)