This is an open-label, dose-escalation, phase I trial of the safety and efficacy of anti-CEA
intraperitoneal CAR-T infusions for treatment in patients with CEA-expressing adenocarcinoma
peritoneal metastases or malignant ascites.
Patients undergo leukapheresis from which peripheral blood mononuclear cells are purified. T
cells are activated and then re-engineered to express chimeric antigen receptors (CARs)
specific for CEA. Cells are expanded in culture and returned to the patient by
intraperitoneal infusion at specific cell doses. One anti-CEA CAR-T dose per patient is
planned. Additional cycles may be administered at the discretion of the principal
investigator. Normal peritoneal and tumor biopsies will be obtained at the time of the CAR-T
infusion, on the final day of the treatment period, and during reporting interval #3.
Inclusion Criteria:
1. Age ≥ 18 years.
2. Must have documented CEA+ carcinomatosis or malignant ascites as demonstrated by an
elevated serum CEA level (≥ 10 ng/mL) or immunohistochemistry on a biopsy or cytologic
specimen (archived tissue is acceptable), for determination of CEA expression. Primary
tumor may be intact and limited liver and/or lung disease permitted.
3. Must have at least evaluable disease by physical examination, serum tumor markers,
radiologic assessment, tumor markers, or laparoscopic visual assessment.
4. Have a life-expectancy ≥ 12 weeks and ECOG performance status ≤ 2.
5. May have low volume of liver metastases defined as < 50% replacement of the liver
volume by metastatic disease, as long as all other eligibility criteria are satisfied.
6. Be willing and able to comply with the study schedule and all other protocol
requirements.
Exclusion Criteria:
1. Female patients of childbearing age will be tested for pregnancy. Pregnant patients
will be excluded from the study. Males who are actively seeking to have children will
be made aware of the unknown risks of this study protocol on human sperm and the need
to practice birth control.
2. Received an investigational study drug within 14 days of leukapheresis or 28 days
before receiving first dose of study drug. Exceptions may be granted with medical
monitor approval.
3. Received any approved anticancer medication within 14 days of leukapheresis or 14 days
before receiving the first dose of study drug. Exceptions may be granted with medical
monitor approval.
4. Have any unresolved toxicity > Grade 2 from previous anticancer therapy, except for
stable chronic toxicities (≤ Grade 3) that are not expected to resolve.
5. Have a history of histologically confirmed metastases outside the peritoneal cavity,
lungs, or liver.
6. Have high volume lung or liver metastases, defined as >5 lung lesions greater than 1
cm in size or ≥ 50% replacement the liver volume by metastatic disease.
7. Received CAR-T, CAR-T cell line, CAR-NK, CAR-pNK, or CAR-NK cell line therapies.
8. Have any of the following laboratory results at Screening (Screening volumes must be
independent of blood product treatment):
1. Hemoglobin ≤ 8.0 g/dL
2. Platelet count < 50 × 109/L
3. Absolute neutrophil count (ANC) < 1.0 × 109/L
9. Untreated or ongoing intra-abdominal infection or bowel obstruction.
10. Have any of the following laboratory results at Screening, regardless of causality:
1. Serum creatinine ≥ 3.0, or estimated creatinine clearance ≤ 30 mL/min and not
dialysis dependent
2. Aspartate aminotransferase (AST) ≥ 4 × upper limit of normal (ULN) and total
bilirubin ≥ 2.0 mg/dL (except for patients in whom hyperbilirubinemia is
attributed to Gilbert's syndrome).
11. Have human immunodeficiency virus (HIV) infection, or hepatitis B virus (HBV) or
hepatitis C virus (HCV) viremia, or are at risk for HBV reactivation (at risk for HBV
reactivation is defined as being HBsAg positive, or anti-HBc-antibody positive), or
are positive for HBV deoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be
undetectable by laboratory test.
12. Are pregnant or breastfeeding.
13. Have active bacterial, viral, or fungal infection: patients with ongoing use of
prophylactic antibiotics, antiviral agents, or antifungal agents remain eligible as
long as there is no evidence of active infection.
14. Has any significant medical condition, laboratory abnormality, or psychiatric illness
that would prevent the patient from participating in the study.
15. Has any condition, including the presence of laboratory abnormalities that places the
patient at an unacceptable risk if the patient was to participate in the study.
16. Left ventricular ejection fraction (LVEF) < 40%
