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Recruiting NCT07219459

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

Phase II Interventional Unresectable or Metastatic Hepatocellular Carcinoma Child-Pugh A Hepatocellular Carcinoma Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Visugromab RDE (recommended dose for expansion), Nivolumab, Lenvatinib, Placebo Saline Infusion.
Who it may be relevant to
Registry conditions: Unresectable or Metastatic Hepatocellular Carcinoma, Child-Pugh A Hepatocellular Carcinoma, Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound. Basic parameters: 18 years — 100 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Germany, Italy, Spain
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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)

Overview

This is a Phase 2b, randomized, blinded clinical 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 HCC and compensated liver function (Child-Pugh A) after failure of 1L treatment that included an anti-PD-(L)1 compound. The trial consists of 2 Parts: a non-randomized Safety-run-in part (Part 1) and the subsequent randomized part (Part 2) with 2 treatment arms (A and B). Randomization of participants into Treatment Arm A and B will continue until 40 efficacy-evaluable participants are enrolled into each Treatment Arm.

Interventions

  • Biological Visugromab RDE (recommended dose for expansion)
    Participants receive visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments
  • Biological Nivolumab
    Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments after visugromab infusion
  • Drug Lenvatinib
    Participants receive Lenvatinib per os (PO) once daily according to body weight (\> 60kg: 12mg; \< 60kg: 8mg)
  • Other Placebo Saline Infusion
    Saline (0.9%NaCl) intravenous (2x IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W) for up to 35 treatments

Primary outcome measures

  • Progression-free survival (PFS) [Time frame: up to 36 months]
Secondary outcome measures (10)
  • Independently assessed PFS by Blinded Independent Central Review (BICR) [Time frame: up to 36 months]
  • CR (Complete Response) rate [Time frame: up to 36 months]
  • PR (Partial Response) rate [Time frame: up to 36 months]
  • ORR (Overall Response) rate [Time frame: up to 36 months]
  • TTR (Time-to-response) rate [Time frame: up to 36 months]
  • PFS (Progression-free survival) rate [Time frame: up to 36 months]
  • Change in body weight (kg) from baseline [Time frame: up to 39 months]
  • Adverse Events [Time frame: up to 60 months]
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100] [Time frame: up to 39 months]
  • Overall survival (OS) [Time frame: up to 60 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Triple blind
Primary purpose
Treatment

Study locations

Spain · 5 centers
  • University Hospital Miguel Servet — Zaragoza
  • Catalan Institute of Oncology, Hospital Duran i Reynals — L'Hospitalet de Llobregat
  • Hospital Clinic of Barcelona — Barcelona
  • University Clinic of Navarra - Pamplona — Pamplona
  • University Hospital Ramon y Cajal — Madrid
United States · 3 centers
  • USC Norris Comprehensive Cancer Center — Los Angeles
  • Peidmont Healthcare, Inc — Atlanta
  • OSF St. Francis Medical Center — Peoria
Germany · 3 centers
  • Hannover Medical School — Hanover
  • University Medical Center of Johannes Gutenberg University Mainz — Mainz
  • Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität — Frankfurt
Italy · 3 centers
  • Polyclinic S. Orsola-Malpighi — Bologna
  • Asst Grande Ospedale Metropolitano Niguarda — Milan
  • Ospedale S.Maria delle Croci — Ravenna

Identifiers

NCT: NCT07219459 · CTL-002-005 · 2025-520675-86-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗