Visugromab, Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure

Main Inclusion Criteria:

• Histologically confirmed diagnosis of unresectable or metastatic HCC, not amenable to a curative treatment approach.
• Measurable disease as per RECIST v1.1 as determined by the Investigator based upon local radiologist assessment.
• Must have failed one line of prior systemic treatment for unresectable or metastatic HCC containing an approved anti PD (L)-1 checkpoint inhibitor (CPI) with a minimum treatment duration of 12 weeks exposure for the CPI with no documented progression in this period.
• Age ≥ 18 years on the day of signing the informed consent.
• Life expectancy of at least 3 months as assessed by the Investigator.
• ECOG performance status ≤1.
• Child-Pugh score of A6 or better.

Main Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma.
• More than 1 line of prior systemic treatment for unresectable or metastatic HCC.
• Received or completed any palliative radiotherapy for symptoms within 28 days of the first dose of IMP.
• Expected to require any other form of antineoplastic therapy during the trial.
• Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
• Known history of other prior malignancy unless participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
• Known or detected clinically active central nervous system (CNS) involvement by HCC or other tumors.
• Have one of the following cardiovascular risk factors: myocardial infarction, peri/myocarditis, or history of ischemic stroke in the past 3 months before planned treatment start, uncontrolled heart failure, uncontrolled ventricular arrhythmia, QT interval corrected for heart rate using Fridericia's formula interval ≥ 470 ms regardless of sex.
• An active autoimmune disease that has required systemic treatment in past 3 months before planned treatment start.
• Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
• Chronic systemic corticosteroid treatment for other reasons.
• Prior liver or other organ transplantation.