et1402l1-artemis™2 t cells in alpha fetoprotein (afp) expressing hepatocellular carcinoma

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

Summary: clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of et1402l1-artemis™2 t cells in patients with alpha fetoprotein positive (afp+ ) hepatocellular carcinoma (hcc).

the molecular target for et1402l1-artemis™2 is human leukocyte antigen (hla) -a02 complexed with a hla-a02-restricted peptide of alpha fetoprotein (afp), which is expressed on 60-80 percent of hepatocellular carcinoma (hcc). artemis™2 is a second generation artemis™ receptor engineered with a human antibody domain against the anti-hla-a02/afp complex. this clinical study evaluates the safety and pharmacokinetics of et1402l1-artemis™2 t-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 intra-hepatic artery (ia) arm or intratumoral injections arm, with the et1402l1-artemis™2 t-cells administered via intrahepatic artery catheter. patients with extrahepatic metastasis will be enrolled in the intravenous (iv) arm, with the et1402l1-artemis™2 t-cells administered through intravenous infusion.

Eligibility criteria:
inclusion criteria: * afp-expressing hcc and serum afp \>100 ng/ml. * abandon or failure in first or second line treatment * molecular hla class i typing confirms participant carries at least one hla-a02 allele * child-pugh score of a or b, barcelona clinic liver cancer stage of c or d * life expectancy \> 4 months * karnofsky score ≥70% * adequate organ function as defined below: 1. patients must have a serum total bilirubin ≤2 x upper limit of normal (uln), alanine transaminase (alt) and aspartate transaminase (ast) ≤5 times the institutional uln. 2. a pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute 3. ejection fraction measured by echocardiogram or multiple gated acquisition scanning (muga) \>45% (evaluation done with 6 weeks of screening does not need to be repeated) 4. diffusing capacity of the lung for carbon monoxide (dlco) or forced expiratory volume in the first second (fev1)\>45% predicted 5. absolute neutrophil count (anc) ≥ 1500/mm3 (10\^9/l) 6. platelet count ≥ 50,000/mm3 (10\^9/l) * 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 tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver. * patients with an organ transplantation history * 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) * 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. * women who are pregnant or breast-feed * hiv-infection