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 (GDFATHERHCC01)

CatalYm

Status and phase: Not yet enrolling; Phase 2

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

Treatments: Other: Placebo Saline Infusion; Biological: Visugromab RDE (recommended dose for expansion); Drug: Tyrosine kinase inhibitor (TKI); Biological: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07219459

CTL-002-005

2025-520675-86-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 104 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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104 participants in 2 patient groups

Arm A

Experimental group

Description:

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

Treatment:

Biological: Nivolumab

Drug: Tyrosine kinase inhibitor (TKI)

Biological: Visugromab RDE (recommended dose for expansion)

Arm B

Active Comparator group

Description:

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

Treatment:

Drug: Tyrosine kinase inhibitor (TKI)

Other: Placebo Saline Infusion