clinical study of et1402l1-car t cells in afp expressing hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma; Liver Cancer; Liver Neoplasms; Metastatic Liver Cancer

Summary: clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of et1402l1-cart-cells in patients with afp+ hcc

the molecular target for et1402l1-cart is alpha fetoprotein (afp), which is expressed on 60-80 percent of hepatocellular carcinoma (hcc). et1402l1-cart is a second generation (cd28/cd3ζ) chimeric antigen receptor (car) engineered with a human single-chain variable antibody fragments (scfv) against the anti-hla-a02/afp complex. this clinical study evaluates the safety and pharmacokinetics of et1402l1-cart-cells in patients with hcc who have no available curative therapeutic options and a poor overall prognosis. patients with lesion(s) localized in liver will be enrolled in the ia arm, with the et1402l1-cart-cells administered via intrahepatic artery catheter. patients with extrahepatic metastasis will be enrolled in the iv arm, with the et1402l1-cart-cells administered through intravenous infusion.

Eligibility criteria:
inclusion criteria: * afp-expressing hcc and serum afp \>100 ng/ml. * measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 20 mm. * molecular hla class i typing confirms participant carries at least one hla-a02 allele * child-pugh score of a or b * life expectancy \> 4 months * age at time of enrollment is ≥18 years of age. * kps ≥70% * adequate organ function as defined below: * a pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute. * patients must have a serum direct bilirubin ≤2 x uln, alt and ast ≤5 times the institutional upper limits of normal. * ejection fraction measured by echocardiogram or muga \>45% (evaluation done within 6 weeks of screening does not need to be repeated) * dlco or fev1 \>45% predicted * absolute neutrophil count (anc) ≥ 1500/mm3 (10\^9/l) * platelet count ≥ 50,000/mm3 (10\^9/l) * negative serum pregnancy test for women with childbearing potential * informed consent/assent: all subjects must have the ability to understand and the willingness to sign a written informed consent. exclusion criteria: * patients with decompensated cirrhosis: child-pugh score c * patients with an organ transplantation history * patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver. * patients with dependence on corticosteroids * patients with active autoimmune diseases requiring systemic immunosuppressive therapy * patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery * patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy) * patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.). * participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled. * patients with other uncontrolled diseases, such as active infections: * acute or chronic active hepatitis b or hepatitis c. * hiv-infection * women who are pregnant

Keywords: alpha-fetoprotein afp hcc car t cell therapy