Child-Pugh A Hepatocellular Carcinoma, Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound, Unresectable or Metastatic Hepatocellular Carcinoma
Conditions
Keywords
CTL-002, Visugromab, GDF-15
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.
Interventions
Participants receive visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments
BIOLOGICALNivolumab
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
DRUGLenvatinib
Participants receive Lenvatinib per os (PO) once daily according to body weight (\> 60kg: 12mg; \< 60kg: 8mg)
Saline (0.9%NaCl) intravenous (2x IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W) for up to 35 treatments
Sponsors
CatalYm GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | up to 36 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| TTR (Time-to-response) rate | up to 36 months | — |
| PFS (Progression-free survival) rate | up to 36 months | — |
| Change in body weight (kg) from baseline | up to 39 months | — |
| Adverse Events | up to 60 months | Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100] | up to 39 months | Assess participants' subjective wellbeing; higher score means better Quality of Life |
| Overall survival (OS) | up to 60 months | — |
Countries
Germany, Italy, Spain, United States
Contacts
CONTACTTomáš Janík, MD
Outcome results
None listed