Treatment of Cabotamig (ARB202) in Advanced Gastrointestinal Cancer Patients

Prior treatment

• Prior gene therapy or therapy with any murine monoclonal antibodies or any murine containing product.
• Active brain, leptomeningeal, or paraspinal metastases, except for asymptomatic metastases and are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent for at least 14 days prior to the start of study interventions.
• Lack of recovery of prior CTCAE Grade 3 or above adverse events due to earlier therapies.
• Chronic use of corticosteroids in excess of \>10mg daily of prednisone or equivalent within 4 weeks prior to alopecia.
• Concomitant use of complementary or alternative medication or therapy such as Chinese herbal medicine.
• Major trauma or major surgery within 4 weeks prior to first dose of study drug

Other illness

• Concurrent treatment with any anticancer agent including chemotherapy, hormonal therapy or radiation therapy. Must be 5 X half-life or 6 weeks (whichever is shorter) post dosing of previous cancer therapies.
• History of allergy or hypersensitivity to murine proteins or study product excipients
• Diagnosis of HIV or chronic active viral hepatitis (HBV, HCV, HIV).
• Active infection requiring systemic treatment.
• Impaired cardiac function (AHA NY Heart Association Grade II-IV) or clinically significant cardiac disease.
• History of Crohn's disease, inflammatory bowel disease, or ulcerative colitis within the past 5 years

Other

• Females who are pregnant, trying to become pregnant, or breastfeeding.
• Abnormal bowel function which would make assessment of bowel permeability difficult to access

• Histologically confirmed colorectal, pancreatic, gastric adenocarcinoma, primary liver cancer or metastatic liver disease, or cholangiocarcinoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Malignancies should possess with ≥10% expression of CDH17 confirmed by immunohistochemistry except for CRC patients. If the testing is based on fine-needle aspiration (FNA) biopsy, the patient will be considered eligible when tumor aspirate demonstrates detectable positive staining cells for CDH17.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Life expectancy \> 3 months.
• Measurable disease as defined by RECIST 1.1 criteria
• Blood coagulation parameters:
  • PT INR ≤ 1.5X ULN
  • PTT INR ≤1.2X ULN
• Patients must have adequate venous peripheral access for apheresis.
• Satisfactory organ and bone marrow function as defined by:
  • absolute neutrophil count \> 1,000/μL
  • platelets \>100,000/μL
  • hemoglobin ≥9 g/dL
  • serum ALT and AST ≤ 3X ULN or AST and ALT ≤5X ULN, if liver function abnormalities are thought to be from underlying malignancy
  • total serum bilirubin ≤ 2X ULN
  • Creatinine \<1.5X ULN
  • Stable amylase for 2 weeks