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

NCT07219459 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CTL-002-0052025-520675-86-00
• Study Type: interventional
• Target: 104
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

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

Keywords

CTL-002; Visugromab; GDF-15

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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.

  up to 36 months

Secondary Outcomes (10)

• Independently assessed PFS by Blinded Independent Central Review (BICR)

  up to 36 months

• CR (Complete Response) rate

  up to 36 months

• PR (Partial Response) rate

  up to 36 months

• ORR (Overall Response) rate

  up to 36 months

• TTR (Time-to-response) rate

  up to 36 months

Other Outcomes (3)

• Maximum concentration (Cmax) of visugromab

  At designated time points (up to 36 months)

• Minimum concentration (Cmin) of visugromab

  At designated time points (up to 36 months)

• Functional Assessment of the Anorexia and Cachexia Therapy questionnaire (FAACT-A/CS)

  up to 39 months

Study Arms (2)

Arm A

EXPERIMENTAL

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

Biological: Visugromab RDE (recommended dose for expansion); Biological: Nivolumab; Drug: Lenvatinib

Arm B

ACTIVE COMPARATOR

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

Drug: Lenvatinib; Other: Placebo Saline Infusion

Interventions

Visugromab RDE (recommended dose for expansion) 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

Also known as: CTL-002

Arm A

Nivolumab 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

Also known as: OPDIVO®

Arm A

Placebo Saline Infusion 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

Also known as: 0.9% NaCl

Arm B

Lenvatinib DRUG

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

Also known as: Lenvima

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CatalYm GmbH: lead

Study Sites (2)

Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität

Frankfurt, 60590, Germany

RECRUITING

Asst Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; lenvatinib; Saline Solution

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Felix Lichtenegger, MD

CONTACT

+49892000664; regulatory-005@catalym.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Throughout the randomized, blinded, placebo-controlled part (Part 2) of the trial, the participants, Investigators, and trial assigned site staff (except for the pharmacists), the clinical CRO (except for the unblinded clinical monitoring team), and imaging vendor will remain blinded to the information which participant is receiving which IMP. The biostatistics provider, central laboratory vendor, safety vendor and Sponsor also remain blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2025
• First Posted: October 21, 2025
• Study Start: March 19, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); IT (1)