CLINICAL TRIAL / NCT06055439
A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy
- Interventional
- Recruiting
- NCT06055439
Contact Information
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
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.
Gender
All
Age Group
18 Years to 85 Years
Accepting Healthy Volunteers
No
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.