A Radioactive Drug (177Lu–PSMA-617) for the Treatment of PSMA Positive Metastatic and/or Unresectable Liver Cancer

Inclusion Criteria

• Subjects must have histologically, cytologically or radiographically confirmed hepatocellular carcinoma by Liver Imaging Reporting and Data System (LI-RADS) with metastatic and/or unresectable disease
• Subjects must have received one prior line of systemic therapy for the treatment of metastatic and/or unresectable HCC including anti-PD-L1 therapy. Subjects 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 subjects < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• 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 creatinine clearance (CrCl) ≥ 60 mL/min using the Cockroft-Gault formula for subjects with creatinine levels > 1.5 upper limit of normal (ULN)
• Child-Pugh class A or B7
• At least one target lesion measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• PSMA-PET demonstrating PSMA PET positive lesion (higher uptake in the tumor compared with background liver uptake)
• Subjects must have the ability to understand and the willingness to sign a written informed consent document
• Subjects of childbearing age are using an appropriate method of contraception

Exclusion Criteria

• Subjects 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 yttrium Y90 (Y90) radioembolization for hepatocellular carcinoma
• Subjects 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
• Subjects 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. Subjects 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
• Subjects 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
• Subjects 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