Phase Ib/II Multicenter Randomized Control Study of Peri-operative Treatment With Combination of CTLA-4, PD-1 Antibodies and Bevacizumab in Resectable HCC (Prophet)

Обзор

The purpose of this phase Ib/II multicenter randomized control study is to investigate the efficacy and safety of peri-operative treatment with combination of CTLA-4, PD-1 antibodies and bevacizumab in resectable HCC

Подробное описание

This study is a prospective, national multi-center clinical trial. Patients with initially resectable hepatocellular carcinoma were randomly assigned to receive neoadjuvant therapy in three groups: IBI310+ sintilimab + bevacizumab (Group A), IBI310+ sintilimab (Group B), and Sintilimab + bevacizumab (Group C).

Вмешательства

• Препарат IBI310+ sintilimab + bevacizumab
  systemic therapy
• Препарат IBI310+ sintilimab
  systemic therapy
• Препарат sintilimab + bevacizumab
  systemic therapy

Первичные конечные точки

• Average depth of pathological response [Срок оценки: 6 months]

Вторичные конечные точки (2)

• 1y-RFS rate [Срок оценки: 12 months]
• 1y-EFS rate [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Written informed consent shall be obtained prior to any trial-related procedures.
• Male or female patients aged ≥18 years and ≤75 years.
• Initial resectable hepatocellular carcinoma (HCC) confirmed by imaging, pathology or cytology.
• No macrovascular tumor thrombus or extrahepatic metastasis detected on imaging examinations.
• Single intrahepatic tumor >5 cm in diameter, or 2-3 intrahepatic tumors with no restriction on tumor diameter (corresponding to CNLC stage Ib-IIa of primary liver cancer in China).
• The maximum tumor diameter < 8 cm.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• Child-Pugh Class A liver function.
• No prior systemic therapy or locoregional therapy for HCC; patients with recurrence ≥2 years after previous curative surgical resection or ablation are eligible for enrollment.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
• Adequate organ function.

Критерии исключения

• Histologically or cytologically confirmed tumors containing components of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other mixed subtypes.
• History of hepatic encephalopathy or prior liver transplantation.
• Currently participating in an interventional clinical trial, or received any investigational medicinal product or investigational device within 4 weeks prior to the first study drug administration.
• Prior receipt of any of the following therapies: anti-PD-1, anti-PD-L1, anti-PD-L2 agents, or agents targeting other T-cell co-stimulatory or co-inhibitory receptors (including but not limited to CTLA-4, OX-40, CD137).
• Received systemic therapy with Chinese patent medicines with anti-tumor indications or immunomodulatory agents (including thymopeptides, interferons, interleukins; excluding local intrapleural administration for controlling pleural effusion) within 2 weeks prior to the first study drug administration.
• History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within 2 years before the first study drug administration. Replacement therapies (e.g., thyroxine, insulin, physiologic corticosteroids for adrenal or pituitary insufficiency) shall not be regarded as systemic treatment.
• Receiving systemic corticosteroid therapy (excluding intranasal, inhaled, or other locally administered corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first study drug administration.

Note: Physiologic doses of corticosteroids (≤10 mg prednisone equivalent per day) are permitted.

• Known history of allogeneic solid organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to any study drug used in this trial.
• Have not fully recovered from toxicities and/or complications induced by any prior intervention before study treatment initiation.
• Known history of human immunodeficiency virus (HIV) infection.
• Untreated active hepatitis B virus (HBV) infection.
• Subjects with active hepatitis C virus (HCV) infection.
• Received any live vaccine within 30 days prior to the first study drug administration (Day 1 of Cycle 1).
• Pregnant or lactating women.
• Presence of any severe or uncontrolled systemic disease.

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

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07714317 · Prophet-IBI310

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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