Visugromab, Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure
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)NivolumabLenvatinibPlacebo 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 (14)
Facility
City
Region
Status
USC Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
Peidmont Healthcare, Inc
Atlanta
Georgia
Recruiting
OSF St. Francis Medical Center
Peoria
Illinois
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
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
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.
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