A Randomized, Multicenter, Double-Blind, Parallel-Controlled Integrated Phase I/III Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of Ipilimumab Biosimilar HLX13 Vs. YERVOY® (US-Sourced YERVOY® and EU-Sourced YERVOY®) As a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 656
- 主要终点
- Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)
研究概览
简要总结
This is a multicenter, randomized, double-blind, parallel-controlled integrated phase I/III clinical study to evaluate the efficacy, safety, PK, and immunogenicity of HLX13 and YERVOY® in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.
详细描述
This study includes three treatment groups. Patients will be randomly assigned at a 2:1:1 ratio to the HLX13, US-sourced YERVOY®, or EU-sourced YERVOY® group to receive the treatment of IMPs in combination with nivolumab.
Patients with good tolerability and disease control will receive HLX13 or YERVOY® in combination with nivolumab on the first day of every 3 weeks for up to 4 cycles. PK and immunogenicity blood sampling will be conducted during the treatment period. After the four treatment cycles, all subjects will be subsequently treated with nivolumab monotherapy until investigator-assessed disease progression, initiation of a new anti-neoplastic therapy, withdrawal of informed consent, death, unacceptable toxicity, or up to 1 year after randomization, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically diagnosed relapsed metastatic or advanced hepatocellular carcinoma not eligible for surgical or locoregional therapies according to the diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD).
- •At least one measurable lesion as assessed by IRRC based on RECIST v1.1 within 4 weeks prior to the first dose in this study.
- •No systemic therapy for relapsed metastatic or advanced hepatocellular carcinoma prior to screening.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •Child-Pugh Class A.
- •Normal major organ functions.
- •Women of childbearing potential should use highly effective methods of contraception during the study and within 5 months after the last study treatment; Male subjects capable of fathering a child must agree to use at least one highly effective method of contraception for the duration of the study and for at least 7 months after the last study treatment.
排除标准
- •With other histopathological types of hepatocellular carcinoma.
- •History of hepatic encephalopathy.
- •Clinically significant ascites.
- •Patients with tumor thrombus at the main portal vein, left or right portal (either or both) vein branch, or inferior vena cava.
- •Presence of the central nervous system disorders at screening, except subjects who have previously received treatment for brain metastases can participate in the study treatment if their clinical symptoms have been stable for at least 4 weeks.
- •Evidence of portal hypertension with bleeding esophageal or gastric varices within 6 months prior to the randomization.
- •Known active or suspected autoimmune diseases.
- •Active co-infection with both hepatitis B and C, or hepatitis D infection in subjects with hepatitis B.
- •Uncontrolled cardiovascular diseases within 6 months.
- •Known interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, and severe lung function abnormalities that may impede the investigators' diagnosis and management of drug-related pulmonary toxicity prior to screening.
- •Patients who have received any T-cell costimulatory agents or immune checkpoint blockade therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other agents that target T cells.
- •Patients who have other conditions not suitable for inclusion per investigator's judgments.
研究组 & 干预措施
HLX13 group
Recombinant anti-CTLA-4 fully human monoclonal antibody injection developed by Shanghai Henlius Biotech, Inc.
干预措施: HLX13 (Drug)
US-sourced YERVOY® group
US-sourced ipilimumab
干预措施: US-sourced YERVOY® (Drug)
EU-sourced YERVOY® group
EU-sourced ipilimumab
干预措施: EU-sourced YERVOY® (Drug)
结局指标
主要结局
Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)
时间窗: Up to Day 21
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss)
时间窗: Up to Day 85
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Best Objective Response Rate (ORR) up to Week 24 (assessed by Independent Radiology Review Committee [IRRC] based on RECIST v1.1)
时间窗: Up to Week 24
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
次要结局
- Maximum serum drug concentration (Cmax) after the first dose(Up to Day 21)
- Trough serum drug concentration (Ctrough) after the first dose(Up to Day 21)
- Time to reach maximum serum drug concentration (Tmax) after the first dose(Up to Day 21)
- Elimination half-life (t1/2) after the first dose(Up to Day 21)
- Total clearance (CL) after the first dose(Up to Day 21)
- Volume of distribution during terminal phase (Vz) after the first dose(Up to Day 21)
- Time to reach maximum serum drug concentration at steady state (Tmax, ss)(Up to Day 85)
- Maximum serum drug concentration at steady state (Cmax, ss)(Up to Day 85)
- Minimum serum drug concentration at steady state (Cmin, ss)(Up to Day 85)
- Elimination half-life (t1/2) at steady state(Up to Day 85)
- Volume of distribution at steady state (Vss)(Up to Day 85)
- Total clearance at steady state (CLss)(Up to Day 85)
- Accumulation ratio of AUC (Rac, AUC)(Up to Day 85)
- Accumulation ratio of Cmax (Rac, Cmax)(Up to Day 85)
- ORR assessed by IRRC (based on RECIST v1.1)(Up to Week 30)
- ORR assessed by investigators (based on RECIST v1.1)(Up to Week 48)
- Duration of Response (DOR) assessed by investigators (based on RECIST v1.1)(Up to Week 48)
- Time to Response (TTR) assessed by investigators (based on RECIST v1.1)(Up to Week 48)
- Progression-Free Survival (PFS) Status assessed by investigators (based on RECIST v1.1)(Up to Week 48)
- Progression-Free Survival Rate (PFSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48(Up to Week 48)
- Overall Survival (OS)(Up to 1 year)
- Overall Survival Rate (OSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48(Up to Week 48)
- Adverse events (AEs)(Up to Month 15)
- Serious adverse events (SAEs)(Up to Month 15)
- Incidence of anti-drug antibodies (ADAs).(Up to 1 year)
- Incidence of neutralizing antibodies (NAbs).(Up to 1 year)