Visugromab plus Nivolumab and Lenvatinib versus Placebo plus Lenvatinib for unresectable or metastatic hepatocellular carcinoma after anti–PD-(L)1 therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 2b, randomized, blinded trial with a non-randomized safety run-in (Part 1) followed by a randomized comparison (Part 2) of visugromab + nivolumab + lenvatinib versus double placebo + lenvatinib. Participants must have unresectable or metastatic hepatocellular carcinoma, compensated liver function (Child‑Pugh A), measurable disease by RECIST v1.1, ECOG 0–1, and prior one-line anti–PD-(L)1–containing systemic therapy. Randomization will continue until there are 40 efficacy‑evaluable participants per arm, and the study will monitor safety and anti-tumor activity. The trial is being run at specialized centers in Europe and is sponsored by CatalYm GmbH.

Why it matters

Who can join: the full rules

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.

Where it's running

• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
  Irvine, California, United States Recruiting
• USC Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• UC Irvine Health. Chao Family Comprehensive Cancer Center
  Orange, California, United States Recruiting
• UCLA Hematology/Oncology - Santa Monica
  Santa Monica, California, United States Recruiting
• Peidmont Healthcare, Inc
  Atlanta, Georgia, United States Recruiting
• OSF St. Francis Medical Center
  Peoria, Illinois, United States Recruiting

Study contacts

• Study coordinator: Tomáš Janík, MD
• Email: regulatory-005@catalym.com
• Phone: +49892000664

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.