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

NCT ID: NCT07219459

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2031-09-30

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.

Conditions

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

Keywords

CTL-002; Visugromab; GDF-15

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A

Visugromab (IV) + Nivolumab intravenous (IV) + TKI (PO)

Group Type: EXPERIMENTAL

Visugromab RDE (recommended dose for expansion)

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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

Tyrosine kinase inhibitor (TKI)

Intervention Type: DRUG

Participants receive the TKI (PO)

Arm B

TKI (PO) + saline (double-placebo) intravenous (IV)

Group Type: ACTIVE_COMPARATOR

Tyrosine kinase inhibitor (TKI)

Intervention Type: DRUG

Participants receive the TKI (PO)

Placebo Saline Infusion

Intervention Type: OTHER

Saline (0.9%NaCl) intravenous (2x IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W) for up to 35 treatments

Interventions

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Tyrosine kinase inhibitor (TKI)

Participants receive the TKI (PO)

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

CTL-002; OPDIVO®; 0.9% NaCl

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CatalYm GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Gerda Vlasitz-Kocks, MD

Role: CONTACT

Phone: +49 89 200066440

Email: regulatory-005@catalym.com

Facility Contacts

Kelsey Lau-Min, MD

Role: primary

Other Identifiers

2025-520675-86-00

Identifier Type: CTIS

Identifier Source: secondary_id

CTL-002-005

Identifier Type: -

Identifier Source: org_study_id