Phase 1b Study of CAR2Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases

Phase 1b Study of the Efficacy and Safety of CAR2 Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases Resistant to Standard Therapy Using the HITM Method and Pressure Enabled Delivery Device

This study is an open-label, single arm phase 1b safety study of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions for pancreatic carcinoma patients with carcinoembryonic antigen positive (CEA+) liver metastases resistant to standard therapy who meet all other eligibility criteria.

Patients will receive weekly 3 doses of CAR2 Anti-CEA CAR-T cells in each 28-day cycle by hepatic arterial infusions using a Pressure Enhanced Delivery Device (PEDD) with low dose systemic IL-2 support. Patients may receive up to 3 cycles of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions, per discretion of the investigator.

All patients who receive investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.

Inclusion Criteria:

• Must have documented CEA+ pancreatic adenocarcinoma liver metastases and have failed greater than or equal to 1 line of conventional systemic therapy.
• Must have at least evaluable liver metastases.
• Must have a life-expectancy at least 12 weeks.
• Patients must be willing and able to comply with the study schedule and all other protocol requirements.
• Females of childbearing potential must have 2 negative pregnancy tests, agree to pregnancy tests during the study, and sexually active female and male patients must be willing to use an effective birth control method to avoid pregnancy.

Exclusion Criteria:

• Subjects who have received an investigational study drug within 14 days of leukapheresis or 28 days before receiving first dose of study drug.
• Subjects who have received any approved anticancer medication within 14 days of leukapheresis or 14 days before receiving the first dose of study drug.
• Have any unresolved toxicity greater than Grade 2 from previous anticancer therapy.
• Have a history of confirmed metastases outside the peritoneal cavity, lungs, or liver.
• More than 50% replacement of one or both liver lobes with tumor.
• Has tumor causing biliary obstruction not amenable to stenting.
• Have a high volume of lung or peritoneal metastases.
• Has received any CAR cell line therapies.
• Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts at screening.
• Has untreated or ongoing intra-abdominal infection or bowel obstruction.
• Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at screening regardless of causality.
• Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
• Female patients who are pregnant or breastfeeding.
• Have active bacterial, viral, or fungal infections.
• Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent study participation.
• Left ventricular ejection fraction (LVEF) < 40%.