Visugromab, Nivolumab and a Tyrosine Kinase Inhibitor (TKI) Compared to Double Placebo and a TKI in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure

Not Applicable

Not yet recruiting

• Conditions: Unresectable or Metastatic Hepatocellular Carcinoma; Failure of First-Line Treatment That Included an Anti PD-(L)1 Compound; Child-Pugh A Hepatocellular Carcinoma
• Interventions: Biological: Visugromab RDE (recommended dose for expansion); Biological: Nivolumab; Other: Placebo Saline Infusion; Drug: Tyrosine kinase inhibitor (TKI)

• Registration Number: NCT07219459
• Lead Sponsor: CatalYm GmbH

Brief Summary

This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and a TKI compared to double placebo and a TKI 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-20
• Study First Submitted QC: 2025-10-20
• Last Update Submitted: 2025-10-20
• Study First Posted: 2025-10-21
• Last Update Posted: 2025-10-21
• Study Start: 2026-02-01
• Primary Completion: 2029-09
• Study Completion: 2031-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 104

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Visugromab RDE (recommended dose for expansion)	Visugromab (IV) + Nivolumab intravenous (IV) + TKI (PO)
Arm A	Nivolumab	Visugromab (IV) + Nivolumab intravenous (IV) + TKI (PO)
Arm A	Tyrosine kinase inhibitor (TKI)	Visugromab (IV) + Nivolumab intravenous (IV) + TKI (PO)
Arm B	Tyrosine kinase inhibitor (TKI)	TKI (PO) + saline (double-placebo) intravenous (IV)
Arm B	Placebo Saline Infusion	TKI (PO) + saline (double-placebo) intravenous (IV)

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
Participant weight course over time	up to 39 months
Overall survival (OS)	up to 60 months
CR (Complete Response) rate	up to 36 months
PFS (Progression-free survival) rate	up to 36 months
Independently assessed PFS by Blinded Independent Central Review (BICR)	up to 36 months
PR (Partial Response) rate	up to 36 months
ORR (Overall Response) rate	up to 36 months	Overall response rate, defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the Investigator
TTR (Time-to-response) rate	up to 36 months
Adverse Events	up to 60 months	Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events
European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC QLQ-C30)	up to 39 months	Assess participants' subjective wellbeing

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States