68Ga-PSMA-11 PET-directed Radioligand Therapy in Metastatic Hepatocellular Carcinoma (HCC)

Inclusion Criteria: * Participants must have histologically, cytologically or radiographically confirmed hepatocellular carcinoma by LI-RADS30 with metastatic and/or unresectable disease. * Participants must have received one prior line of systemic therapy for the treatment of metastatic and/or unresectable HCC including anti-PD-L1 therapy. Participants will be enrolled at the time of progression on first-line therapy for metastatic and/or unresectable disease. * Age \>18 years. Because no dosing or adverse event data are currently available on the use of 177Lu-PSMA-617 (Lu-177 vipivotide tetraxetan) in participants \<18 years of age, children are excluded from this study. * ECOG performance status 0 or 1. * Participants must have normal organ and marrow function as defined below: Absolute Neutrophil Count ≥ 1,500/mcL. Hemoglobin \> 9 g/dL. Platelet count ≥ 75,000/mcL. Serum creatinine ≤ 1.5 x institutional upper limit of normal or CrCl ≥60 mL/min using the Cockroft-Gault formula for participants with creatinine levels \>1.5 ULN. Child-Pugh class A or B7. * At least one target lesion measurable by RECIST 1.1 criteria. * PSMA-PET demonstrating PSMA PET positive lesion (higher uptake in the tumor compared with background liver uptake). * Participants must have the ability to understand and the willingness to sign a written informed consent document. * Participants of childbearing age are using an appropriate method of contraception. Exclusion Criteria: * Participants receiving any other investigational agents. * Subject has received investigational therapy within 4 weeks or within 5 half-lives of the therapeutic agent (whichever is shorter). * Ongoing grade 3 or higher toxicity from prior anticancer systemic therapy. * Prior treatment with Y90 radioembolization for hepatocellular carcinoma. * Participants who have undergone major surgery within 3 months of screening and have not adequately recovered. * Known additional malignancy that currently requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. * Participants with untreated brain metastases and/or carcinomatous meningitis will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases and are not using steroids for at least 7 days prior to trial treatment. * Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Participants with known psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the treating investigator. * Subject is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months for females and 14 weeks for males after the last dose of trial treatment. Pregnant or breastfeeding women are excluded from this study because 177Lu-PSMA-617 has not been previously studied in this population and the potential for teratogenic or abortifacient effects are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to the treatment of the mother with 177Lu-PSMA-617, breastfeeding should be discontinued if the mother is treated with 177Lu-PSMA-617. These potential risks may also apply to 68Ga-PSMA-11 used in this study. * Subject has received live vaccine within 30 days prior to the first dose of trial treatment. * Subject with recent variceal bleeding, gastrointestinal bleeding or high risk of bleeding.