Visugromab, Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure (GDFATHERHCC01)

A Phase 2b, Randomized, Blinded 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 Hepatocellular Carcinoma and Compensated Liver Function (Child-Pugh A) After Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound (GDFATHER HCC-01)

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.

Study Overview

• Status: Recruiting
• 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
• Intervention / Treatment: Biological: Visugromab RDE (recommended dose for expansion); Biological: Nivolumab; Other: Placebo Saline Infusion; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tomáš Janík, MD; Phone Number: 31 +49892000664; Email: regulatory-005@catalym.com

Study Locations

• Germany
  • Frankfurt, Germany, 60590
    • Recruiting
    • Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität
    • Contact: Jörg Trojan, Prof.; Phone Number: +4969630187769; Email: trojan@em.uni-frankfurt.de
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Recruiting
      • Hannover Medical School
      • Contact: Anna Saborowski, PD Dr. med.; Phone Number: +495115329592; Email: Saborowski.Anna@mh-hannover.de
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Recruiting
      • University Medical Center of Johannes Gutenberg University Mainz
      • Contact: Peter R. Galle, Prof. Dr. med.; Phone Number: +49 (0) 6131 17 7276; Email: galle@uni-mainz.de
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Polyclinic S. Orsola-Malpighi
    • Contact: Fabio Piscaglia, MD; Phone Number: +39 0512142477; Email: fabio.piscaglia@unibo.it
  • Milan, Italy, 20162
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
    • Contact: Katia Bencardino, Dr.; Phone Number: +390264442291; Email: oncologia@ospedaleniguarda.it
• Spain
  • Aragon
    • Zaragoza, Aragon, Spain, 50009
      • Recruiting
      • University Hospital Miguel Servet
      • Contact: Roberto Pazo Cid, Dr.; Phone Number: +34 (976) 765 500; Email: rpazo@salud.aragon.es
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Recruiting
      • Hospital Clinic of Barcelona
      • Contact: María Reig, Dr; Phone Number: +34 932279235; Email: MREIG1@clinic.cat
  • Chartered Community of Navarra
    • Pamplona, Chartered Community of Navarra, Spain, 31008
      • Recruiting
      • University Clinic of Navarra - Pamplona
      • Contact: Bruno Sangro Gomez-Acebo; Phone Number: +34 948 255 400; Email: bsangro@unav.es
  • Madrid
    • Madrid, Madrid, Spain, 28034
      • Recruiting
      • University Hospital Ramon y Cajal
      • Contact: José Luis Lledó Navarro; Phone Number: +34 913368592; Email: jllledo63@yahoo.es
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Contact: Anthony El-Khoueiry, Dr; Phone Number: +1 (323) 865 3000; Email: elkhouei@med.usc.edu
      • Contact: Charlean Ketchens; Phone Number: +1 (323) 865 3000; Email: ketchens_c@med.usc.edu
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Peidmont Healthcare, Inc
      • Contact: Sope Olugbile, MD; Phone Number: 404 (425) 1777; Email: sope.olugbile@piedmont.org
      • Contact: Karma MCcants; Phone Number: 404 (605) 2366; Email: karma.mccants@piedmont.org
  • Illinois
    • Peoria, Illinois, United States, 61637
      • Recruiting
      • OSF St. Francis Medical Center
      • Contact: Robert McWilliams, Dr.; Email: Robert.R.McWilliams@osfhealthcare.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Visugromab (IV) + Nivolumab intravenous (IV) + Lenvatinib (PO)	Biological: 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; Other Names: CTL-002; 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; Other Names: OPDIVO®; Drug: Lenvatinib; Participants receive Lenvatinib per os (PO) once daily according to body weight (> 60kg: 12mg; < 60kg: 8mg); Other Names: Lenvima
Active Comparator: Arm B; Lenvatinib (PO) + saline (double-placebo) intravenous (IV)	Other: 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; Other Names: 0.9% NaCl; Drug: Lenvatinib; Participants receive Lenvatinib per os (PO) once daily according to body weight (> 60kg: 12mg; < 60kg: 8mg); Other Names: Lenvima

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		up to 60 months
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	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	up to 36 months
TTR (Time-to-response) rate		up to 36 months
PFS (Progression-free survival) rate		up to 36 months
Adverse Events	Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events	up to 60 months
Change in body weight (kg) from baseline		up to 39 months
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100]	Assess participants' subjective wellbeing; higher score means better Quality of Life	up to 39 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax) of visugromab	Cmax is the maximum observed serum concentration of visugromab	At designated time points (up to 36 months)
Minimum concentration (Cmin) of visugromab	Cmin is the minimum observed serum concentration of visugromab	At designated time points (up to 36 months)
Functional Assessment of the Anorexia and Cachexia Therapy questionnaire (FAACT-A/CS)	FAACT-ACS consists of 12 items assessing anorexia/cachexia-related symptoms. Each item is scored individually from 0 ("Not at all") to 4 ("Very much"), with some requiring reverse scoring as in the FAACT Scoring Guideline. The FAACT-ACS subscale score is calculated by summing item scores (reversals performed as applicable); multiplied by the total number of items and divided by the number of items answered. The total score ranges from 0-48, with higher scores indicating better anorexia/cachexia-related quality of life.	up to 39 months

Collaborators and Investigators

• Sponsor: CatalYm GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: October 20, 2025
• First Submitted That Met QC Criteria: October 20, 2025
• First Posted (Actual): October 21, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; Visugromab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Pharmaceutical Preparations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Nivolumab; Saline Solution; lenvatinib
• Other Study ID Numbers: CTL-002-005; 2025-520675-86-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No