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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 660
- 试验地点
- 37
- 主要终点
- Stage 1: Best Overall Response (BOR) per Investigator
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Prior systemic therapy for HCC.
- •Symptomatic, untreated, or actively progressing CNS metastases.
- •History of malignancy other than HCC.
研究组 & 干预措施
Stage 1: Cohort 1
Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Livmoniplimab (Drug)
Stage 1: Cohort 1
Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Budigalimab (Drug)
Stage 1: Cohort 2
Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Livmoniplimab (Drug)
Stage 1: Cohort 2
Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Budigalimab (Drug)
Stage 1: Cohort 3 - Group 1 (Control)
Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 3 - Group 1 (Control)
Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Bevacizumab (Drug)
Stage 1: Cohort 3 - Group 2 (Control)
Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met.
干预措施: Durvalumab (Drug)
Stage 1: Cohort 3 - Group 2 (Control)
Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met.
干预措施: Tremelimumab (Drug)
Stage 2: Arm 1
Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Livmoniplimab (Drug)
Stage 2: Arm 1
Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.
干预措施: Budigalimab (Drug)
Stage 2: Arm 2 (Control)
Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.
干预措施: Durvalumab (Drug)
Stage 2: Arm 2 (Control)
Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Stage 1: Best Overall Response (BOR) per Investigator
时间窗: Through Study Completion, Up to Approximately 56 Months
BOR is defined as a participant achieving confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by investigators at any time prior to subsequent anticancer therapy.
Stage 2: Overall Survival (OS)
时间窗: Through Study Completion, Up to Approximately 56 Months
OS is defined as the time from randomization until death from any cause
次要结局
- Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab(Through Study Completion, Up to Approximately 56 Months)
- Stage 2: Number of Participants with Progression-Free Survival (PFS)(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)(Baseline to Week 12)
- Stage 1: Overall Survival (OS)(Through Study Completion, Up to Approximately 56 Months)
- Stage 1: Time to Cmax (Tmax) of Livmoniplimab and Budigalimab(Through Study Completion, Up to Approximately 56 Months)
- Stage 1: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab(Through Study Completion, Up to Approximately 56 Months)
- Change from Baseline in the Fatigue Domain of the EORTC QLQ-HCC18(Baseline to Week 12)
- Stage 1: Number of Participants with Progression-Free Survival (PFS)(Through Study Completion, Up to Approximately 56 Months)
- Stage 1: Duration of Response (DOR) per Investigator(Through Study Completion, Up to Approximately 56 Months)
- Stage 1: Number of Participants with Adverse Events (AEs)(Through Study Completion, Up to Approximately 56 Months)
- Stage 2: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) per BICR(Through Study Completion, Up to Approximately 56 Months)
- 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)(Baseline to Week 12)
- Change from Baseline in Global Health Status (GHS)/Quality of Life (QoL) Domain as Measured by the GHS/QoL Domain of the EORTC QLQ-C30(Baseline to Week 12)