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Recruiting Phase 2

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

NCT07219459 · tracked via the Priya Life Science Italy tracker
Phase
Phase 2
Started
2026-03-19
Last updated
2026-09-23

Condition(s) studied

Unresectable or Metastatic Hepatocellular CarcinomaChild-Pugh A Hepatocellular CarcinomaFailure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound

Investigational drug(s) / intervention(s)

Visugromab RDE (recommended dose for expansion) →Nivolumab →Lenvatinib →Placebo Saline Infusion

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

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

Lenvatinib: Participants receive Lenvatinib per os (PO) once daily according to body weight (\> 60kg: 12mg; \< 60kg: 8mg)

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

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
100 Years
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Progression-free survival (PFS) — up to 36 months
    Investigator assessed Progression-free survival (PFS) time from randomization (during Safety Run-In: initiation of treatment) to first documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first.

Trial sites (23)

FacilityCityRegionStatus
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care Irvine California Recruiting
USC Norris Comprehensive Cancer Center Los Angeles California Recruiting
UC Irvine Health. Chao Family Comprehensive Cancer Center Orange California Recruiting
Peidmont Healthcare, Inc Atlanta Georgia Recruiting
OSF St. Francis Medical Center Peoria Illinois Recruiting
Massachusetts General Hospital Boston Massachusetts Recruiting
Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque Pessac France Recruiting
Poitiers University Hospital Center - Miletrie Hospital Poitiers France Recruiting
Gustave Roussy Villejuif France Recruiting
Hannover Medical School Hanover Lower Saxony Recruiting
University Medical Center of Johannes Gutenberg University Mainz Mainz Rhineland-Palatinate Recruiting
Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität Frankfurt Germany Recruiting
Polyclinic S. Orsola-Malpighi Bologna Italy Recruiting
Ospedale San Raffale, IRCCS Milan Italy Recruiting
Asst Grande Ospedale Metropolitano Niguarda Milan Italy Recruiting
Ospedale S.Maria delle Croci Ravenna Italy Recruiting
University Hospital Miguel Servet Zaragoza Aragon Recruiting
Catalan Institute of Oncology, Hospital Duran i Reynals L'Hospitalet de Llobregat Barcelona Recruiting
Hospital Clinic of Barcelona Barcelona Catalonia Recruiting
University Clinic of Navarra - Pamplona Pamplona Chartered Community of Navarra Recruiting
University Hospital Ramon y Cajal Madrid Madrid Recruiting
Western General Hospital Edinburgh United Kingdom Recruiting
King's College Hospital London United Kingdom Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07219459 on ClinicalTrials.gov ↗ ← All trials in Italy