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Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
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.

Arm Groups

ArmDescriptionAssigned Intervention
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)
  • Drug: Lenvatinib
    Participants receive Lenvatinib per os (PO) once daily according to body weight (> 60kg: 12mg; < 60kg: 8mg)
    Other names:
    • Lenvima
  • 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

Recruiting Locations

USC Norris Comprehensive Cancer Center
Los Angeles, California 90033
Contact:
Anthony El-Khoueiry, Dr
+1 (323) 865 3000
elkhouei@med.usc.edu

Peidmont Healthcare, Inc
Atlanta, Georgia 30309
Contact:
Sope Olugbile, MD
404 (425) 1777
sope.olugbile@piedmont.org

OSF St. Francis Medical Center
Peoria, Illinois 61637
Contact:
Robert McWilliams, Dr.
Robert.R.McWilliams@osfhealthcare.org

More Details

Status
Recruiting
Sponsor
CatalYm GmbH

Study Contact

Tomáš Janík, MD
+49892000664
regulatory-005@catalym.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.