A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

Exclusion Criteria

• •Inability to comply with study and follow-up procedures.
• •Women who are pregnant or lactating.
• •Has BRAF-mutated colorectal cancer.
• •Has received trifluridine/tipiracil (TAS-102) or regorafenib for metastatic disease.
• •Treatment with chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy (excluding bridging therapy) within 4 weeks prior to the lymphodepletion start date.
• •Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent in the previous 28 days prior to enrolment.
• •Have received antibody-based therapies within the previous 28 days or 5 half-lives of the agent, whichever is shorter.
• •Major surgery, in the previous 4 weeks prior to enrolment.
• •Clinically detectable pleural effusion requiring drainage in the 4 weeks prior to enrolment.
• •Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the subject to provide informed consent, receive protocol therapy or may impose excessive risk to the subject.
• •Known central nervous system (CNS) disease.
• •Current use of medications that may have the potential of QTc prolongation.
• •Uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
• •Has a known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
• •Inability to be venipunctured and/or tolerate venous access.
• •Second malignancies within 5 years prior to enrollment, except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent.
• •Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of ≤10 mg/day prednisone.
• •History of inflammatory bowel disease (active or past) or active peptic ulcer disease.
• •History of connective tissue disorders.
• •History of chronic leukemias.
• •History of previous, whole abdomen radiation therapy (or total pelvic radiation therapy) or more than Grade 1 residual toxicity from previous radiation therapy.
• •High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year
• •Left ventricular ejection fraction \<50%.
• •Have had a venous thromboembolic event requiring anticoagulation.
• •Congenital or acquired long QT syndrome.
• •QTc prolongation.
• •History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• •Patients with ascites, previous drainage of ascites, peritoneal caking, and/or significant peritoneal deposits at Baseline are excluded from participation in the study
• •Patients with reduced liver reserves and/or possibility of hepatobiliary complications, including, but not limited to; portal hypertension, liver resection (segmentectomy, metastasectomy) in the previous 6 months, patients with existing biliary stents or the need to receive a biliary stent to relieve bile duct obstruction of any etiology, patients with cholelithiasis, patients who abuse alcohol or paracetamol (with or without concomitant alcohol abuse), patients who use herbal medicines, and patients with substance abuse.