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

Официальное название

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)

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Progression-free survival (PFS) [Срок оценки: up to 36 months]

Вторичные конечные точки (10)

• Independently assessed PFS by Blinded Independent Central Review (BICR) [Срок оценки: up to 36 months]
• CR (Complete Response) rate [Срок оценки: up to 36 months]
• PR (Partial Response) rate [Срок оценки: up to 36 months]
• ORR (Overall Response) rate [Срок оценки: up to 36 months]
• TTR (Time-to-response) rate [Срок оценки: up to 36 months]
• PFS (Progression-free survival) rate [Срок оценки: up to 36 months]
• Change in body weight (kg) from baseline [Срок оценки: up to 39 months]
• Adverse Events [Срок оценки: up to 60 months]
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100] [Срок оценки: up to 39 months]
• Overall survival (OS) [Срок оценки: up to 60 months]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Испания · 5 центров

• University Hospital Miguel Servet — Zaragoza
• Catalan Institute of Oncology, Hospital Duran i Reynals — L'Hospitalet de Llobregat
• Hospital Clinic of Barcelona — Barcelona
• University Clinic of Navarra - Pamplona — Pamplona
• University Hospital Ramon y Cajal — Madrid

США · 3 центра

• USC Norris Comprehensive Cancer Center — Los Angeles
• Peidmont Healthcare, Inc — Atlanta
• OSF St. Francis Medical Center — Peoria

Германия · 3 центра

• Hannover Medical School — Hanover
• University Medical Center of Johannes Gutenberg University Mainz — Mainz
• Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität — Frankfurt

Италия · 3 центра

• Polyclinic S. Orsola-Malpighi — Bologna
• Asst Grande Ospedale Metropolitano Niguarda — Milan
• Ospedale S.Maria delle Croci — Ravenna

Идентификаторы

NCT: NCT07219459 · CTL-002-005 · 2025-520675-86-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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