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

A Phase 2b, Randomized, Blinded Trial Investigating the Efficacy and Safety of Visugromab in Combination With Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Participants With Unresectable or Metastatic Hepatocellular Carcinoma and Compensated Liver Function (Child-Pugh A) After Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound (GDFATHER HCC-01)

This trial will test whether adding visugromab and nivolumab to lenvatinib helps people with unresectable or metastatic liver cancer whose disease progressed after an anti–PD-(L)1 treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: CatalYm GmbH (Industry-sponsored)
• Drugs / interventions: visugromab, nivolumab, Lenvatinib
• Locations: 2 sites (Frankfurt and 1 other locations)
• Trial ID: NCT07219459 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adults with unresectable or metastatic hepatocellular carcinoma, Child‑Pugh A liver function, ECOG performance status 0–1, measurable disease, and prior single-line treatment that included an approved anti–PD-(L)1 agent are the intended candidates.

Not a fit: Patients with fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma histology, more than one prior systemic therapy, decompensated liver disease (Child‑Pugh B/C), or recent palliative radiotherapy are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could overcome resistance to prior PD-(L)1 therapy and extend time without disease progression or improve survival for patients with advanced HCC.

How similar studies have performed: Combinations of PD‑1/PD‑L1 inhibitors with tyrosine kinase inhibitors have shown promising activity in HCC, but targeting GDF‑15 with visugromab is a novel approach with limited clinical data to date.

Eligibility criteria

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 this trial is running

Frankfurt and 1 other locations

• Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität — Frankfurt, Germany (Recruiting)
• Asst Grande Ospedale Metropolitano Niguarda — Milan, Italy (Recruiting)

Study contacts

• Study coordinator: Felix Lichtenegger, MD

Conditions Unresectable or Metastatic Hepatocellular Carcinoma; Child-Pugh A Hepatocellular Carcinoma; Failure of First-Line Treatment That Included an Approved Anti PD-1 Compound; CTL-002; Visugromab; GDF-15