GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

Inclusion Criteria

• •Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology
• •Participants must:
• •* have progressed on at least 1 prior line of treatment
• •OR
• •-been intolerant of at least 1 prior line of treatment.
• •Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators.
• •Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy
• •Participants must have at least 1 measurable lesion by RECIST version 1.1
• •Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation.
• •Age \>= 18 years.
• •Performance status (ECOG) 0-1
• •Participants must have adequate organ and marrow function as defined below:
• •ANC: \>= 1,000/mcL
• •Platelets: \>= 75,000/mcL
• •Hemoglobin: \>= 8 g/dL
• •total bilirubin: If cirrhosis present: Part of Child Pugh requirement
• •If no cirrhosis: bilirubin should be \<= 1.5 x ULN
• •ALT or AST: \<= 5 x ULN.
• •Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl) (A): \< 1.5x institution upper limit of normal OR \>= 50 mL/min/1.73 m\^2 for participant with creatinine levels, \>= 1.5 X institutional ULN
• •ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);
• •AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• •(A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.
• •Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation.
• •Room air oxygen saturation of 92% or greater.
• •Treatment-related toxicities must be resolved to \<= grade 1.
• •For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment.
• •The study drugs are harmful to developing human fetus. For this reason, women of childbearing potential must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period.
• •HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring.
• •Participants must be able to understand and be willing to sign a written informed consent.
• •For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts