A Study to Assess the Dose, Adverse Events, and Change in Disease Activity of Livmoniplimab as an Intravenous (IV) Solution in Combination With Budigalimab as an IV Solution in Adult Participants With Hepatocellular Carcinoma (HCC)

Официальное название

A Phase 2/3, Randomized Study to Evaluate the Dose Optimization, Safety, and Efficacy of Livmoniplimab in Combination With Budigalimab in Subjects With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) Who Have Not Previously Received Systemic Treatment

Обзор

Hepatocellular carcinoma (HCC) is a common cancer worldwide and a leading cause of cancer-related death. The majority of participants first presenting with HCC have advanced unresectable or metastatic disease. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab. Livmoniplimab is an investigational drug being developed for the treatment of HCC. There are 2 stages to this study. In Stage 1, there are 3 treatment arms and participants will be randomized in a 1:1:1 ratio. Participants will either receive livmoniplimab (at different doses) in combination with budigalimab (another investigational drug), atezolizumab in combination with bevacizumab, or tremelimumab in combination with durvalumab. In Stage 2, there are 2 treatments arms and participants will be randomized in a 1:1 ratio. Participants will either receive livmoniplimab (optimized dose) in combination with budigalimab or tremelimumab in combination with durvalumab. Approximately 660 adult participants will be enrolled in the study across 185 sites worldwide. Stage 1: In arm 1, participants will receive intravenously (IV) infused livmoniplimab (Dose 1) in combination with IV infused budigalimab, every 3 weeks. In arm 2, participants will receive IV infused livmoniplimab (Dose 2) in combination with IV infused budigalimab, every 3 weeks. In Arm 3 (control), participants will receive the investigator's choice: IV atezolizumab in combination with IV bevacizumab every 3 weeks or single dose IV tremelimumab in combination with IV durvalumab every 4 weeks. Stage 2: In arm 1, participants will receive IV infused livmoniplimab (optimized dose) in combination with IV infused budigalimab, every 3 weeks. In Arm 2 (control), participants will receive single dose IV tremelimumab in combination with IV durvalumab every 4 weeks. All participants will continue treatment until disease progression or discontinuation criteria are met, whichever occurs first. The estimated duration of this study is about 56 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.

Вмешательства

• Препарат Livmoniplimab
  Intravenous (IV) Solution
• Препарат Budigalimab
  Intravenous (IV) Solution
• Препарат Durvalumab
  Intravenous (IV) Solution
• Препарат Atezolizumab
  Intravenous (IV) Solution
• Препарат Bevacizumab
  Intravenous (IV) Solution
• Препарат Tremelimumab
  Intravenous (IV) Solution

Первичные конечные точки

• Stage 1: Best Overall Response (BOR) per Investigator [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 2: Overall Survival (OS) [Срок оценки: Through Study Completion, Up to Approximately 56 Months]

Вторичные конечные точки (12)

• Stage 1: Number of Participants with Progression-Free Survival (PFS) [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Duration of Response (DOR) per Investigator [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Overall Survival (OS) [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Number of Participants with Adverse Events (AEs) [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Time to Cmax (Tmax) of Livmoniplimab and Budigalimab [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 1: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 2: Number of Participants with Progression-Free Survival (PFS) [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Stage 2: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) per BICR [Срок оценки: Through Study Completion, Up to Approximately 56 Months]
• Change from Baseline in the Pain Domain of the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-Question Module (EORTC QLQ-HCC18) [Срок оценки: Baseline to Week 12]
• Change from Baseline in the Fatigue Domain of the EORTC QLQ-HCC18 [Срок оценки: Baseline to Week 12]
• Change from Baseline in Physical Function (PF) Domain of the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) [Срок оценки: Baseline to Week 12]

Критерии участия

Критерии включения

• Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology or cytology or clinically by American Association for the Study of Liver Diseases criteria for participants with cirrhosis.
• Barcelona Clinic Liver Cancer (BCLC) Stage B or C.
• Child-Pugh A or B7 classification (i.e., total Child-Pugh score of 5, 6, or 7).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

Критерии исключения

• Prior systemic therapy for HCC.
• Symptomatic, untreated, or actively progressing CNS metastases.
• History of malignancy other than HCC.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• City of Hope /ID# 261468 — Duarte
• City of Hope at Orange County Lennar Foundation Cancer Center /ID# 261669 — Irvine
• UC Irvine /ID# 255673 — Orange
• The University of Chicago Medical Center /ID# 255674 — Chicago
• Alliance for Multispecialty Research LLC Kansas City Oncology /ID# 256830 — Merriam
• Norton Cancer Institute /ID# 260775 — Louisville
• Henry Ford Hospital /ID# 255803 — Detroit
• Metro Minnesota Community Oncology Research Consortium (MMCORC) /ID# 256041 — Saint Louis Park
• … и ещё 5 центров

Италия · 7 центров

• IRCCS Istituto Clinico Humanitas /ID# 256684 — Rozzano
• IRCCS Ospedale San Raffaele /ID# 256404 — Milan
• P.O. Ospedale del Mare /ID# 256410 — Naples
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 2655 — Rome
• IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 256412 — Bologna
• Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone /ID# 256681 — Palermo
• Fondazione Policlinico Universitario Campus Bio-Medico /ID# 256895 — Roma

Испания · 7 центров

• Hospital Universitario Marques de Valdecilla /ID# 255769 — Santander
• Hospital Universitario Reina Sofia /ID# 255779 — Córdoba
• Hospital Universitario Puerta de Hierro - Majadahonda /ID# 255778 — Majadahonda
• Hospital Universitario Vall d'Hebron /ID# 255771 — Barcelona
• Hospital General Universitario Gregorio Maranon /ID# 255772 — Madrid
• Hospital Universitario Virgen del Rocio /ID# 255776 — Seville
• Hospital Universitario Miguel Servet /ID# 255774 — Zaragoza

Тайвань · 5 центров

• National Taiwan University Hospital /ID# 256168 — Taipei City
• China Medical University Hospital /ID# 256764 — Taichung
• Taichung Veterans General Hospital /ID# 259405 — Taichung
• National Cheng Kung University Hospital /ID# 256766 — Tainan
• Taipei Veterans General Hosp /ID# 256169 — Taipei

Франция · 4 центра

• CHU Grenoble - Hopital Michallon /ID# 256627 — La Tronche
• Institut Gustave Roussy /ID# 258460 — Villejuif
• Hôpital Avicenne /ID# 266005 — Bobigny
• Hopital Beaujon /ID# 256551 — Clichy

Пуэрто-Рико · 1 центр

• Puerto Rico Medical Research Center /ID# 262362 — Hato Rey

Идентификаторы

NCT: NCT06109272 · M24-052 · 2023-504600-28-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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