Amplitude-modulated Radiofrequency Electromagnetic Field Treatment for Advanced Hepatocellular Carcinoma (Immune-RF)

Inclusion Criteria:

• Treatment with combined Anti-PD-L1 and Anti-CTLA-4 antibodies

• Written informed consent prior to any study procedure

• 18 years or older

• Histologically confirmed HCC

• HCC not amenable to curative (including resection or ablation) or locoregional (including TACE) therapies

• No prior systemic therapy for HCC

• Compensated liver function, as defined by a Child-Pugh score ≤ B7

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Measurable disease by Response Criteria in Solid Tumors (mRECIST and RECIST v1.1)criteria

• Body weight of > 30 kg

• Women of childbearing potential with negative pregnancy test and agreement foradequate birth control if conception is possible

• If present HBV and HCV managed according to the local institutional practice

Exclusion criteria:

• Arterioembolic event including a stroke or myocardial infarction within 3 monthsprior to randomization Severe / unstable angina, or symptomatic congestive heartfailure as defined by NYHA III/IV

• Cardiac pacemakers / ICD

• Large metal implants in the treatment area

• Current evidence of coagulopathy or bleeding diathesis

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

• Decompensated liver function as defined by Child Pugh ≥ B8

• Patients on a liver transplantation list

• Patients with autoimmune disorders or history of organ transplantation who requireimmunosuppressive therapy

• Uncontrolled autoimmune or inflammatory disorders

• Patient not able for supine positioning (e.g. due to pain)

• Significantly altered mental status

• Pregnancy and breastfeeding