Evaluating a new CAR T-cell therapy for advanced gastrointestinal cancers
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
This study is testing a new CAR T-cell therapy to see if it can help people with advanced gastrointestinal cancers that haven't improved with other treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 135 (estimated) |
| Ages | 18 Years to 85 Years |
| Sex | All |
| Sponsor | Chimeric Therapeutics Industry-sponsored |
| Drugs / interventions | cyclophosphamide, fludarabine, prednisone, CAR T, chemotherapy |
| Locations | 4 sites (Atlanta, Georgia and 3 other locations) |
| Trial ID | NCT06055439 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to assess the safety and efficacy of CHM-2101, an autologous CDH17 CAR T-cell therapy, for patients with advanced gastrointestinal cancers that have not responded to standard treatments. The study is divided into two phases: Phase 1 focuses on dose escalation and expansion, while Phase 2 evaluates the therapy's effectiveness. Participants will undergo leukapheresis to collect their own T cells, which will then be modified and expanded in the lab before being infused back into the patient. The trial includes specific eligibility criteria to ensure that participants have the appropriate tumor types and treatment history.
Who should consider this trial
Good fit: Ideal candidates include patients with advanced gastric or colorectal cancers, or specific neuroendocrine tumors who have failed at least one prior treatment.
Not a fit: Patients with early-stage cancers or those who have not received prior systemic treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced gastrointestinal cancers that are resistant to existing therapies.
How similar studies have performed: Other studies using CAR T-cell therapies for various cancers have shown promising results, indicating potential for success in this novel application.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Documented informed consent of the participant and/or legally authorized representative.
2. Confirmed histologic diagnosis of one of the following solid tumors of GI origin:
1. Gastric adenocarcinoma Note: for gastric adenocarcinoma patients only, central laboratory confirmation of CDH17+ tumor expression is required.
2. Colon and/or rectal adenocarcinoma
3. G1, G2, and well-differentiated G3 neuroendocrine tumors of the midgut and hindgut (ileal, jejunal, cecal, distal colonic, or rectal; with ≤ 55% Ki67 expression)
3. 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.
4. 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.
5. Age ≥ 18 years and ≤ 85 years.
6. 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).
7. Eastern Cooperative Oncology Group (ECOG) ≤ 1.
8. Life expectancy ≥ 12 weeks.
9. No known contraindications to leukapheresis, cyclophosphamide, fludarabine, or steroids.
10. 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
11. Left ventricular ejection fraction ≥ 50%.
12. Seronegative for human immunodeficiency virus (HIV) by antigen/antibody (Ag/Ab) testing.
13. Seronegative for hepatitis B and/or hepatitis C virus.
14. 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.
15. 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:
1. Previous treatment with CDH17-targeted therapies.
2. 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).
3. Uncontrolled seizure activity and/or known central nervous system (CNS) metastases.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
5. 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.
6. Liver involvement ≥ 50%.
7. Active infection requiring oral or IV antibiotics.
8. Current diagnosis of pleural effusions, interstitial lung disease, or heart failure of New York Heart Association Classification of Heart Failure Class III or IV.
9. 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).
10. No prior malignancy within 5 years except for non-melanomatous skin cancer or cervical cancer treated with curative intent
11. Currently breastfeeding or planning to become pregnant within 9 months of study enrollment.
12. 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.
Where this trial is running
Atlanta, Georgia and 3 other locations
- Emory University — Atlanta, Georgia, United States (Recruiting)
- University of Chicago — Chicago, Illinois, United States (Recruiting)
- University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
- Sarah Cannon Research Institute — Nashville, Tennessee, United States (Recruiting)
Study contacts
- Principal investigator: Jennifer Eads, MD — University of Pennsylvania
- Study coordinator: Chimeric Clinical
- Email: clinical@chimerictherapeutics.com
- Phone: (323) 366-9009
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.