NCT06530251招募中1 期
A Phase Ib/II Study of AK112 in Combination Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)
Akeso2 个研究点 分布在 1 个国家目标入组 280 人开始时间: 2024年9月24日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 280
- 试验地点
- 2
- 主要终点
- Number of subjects with dose limiting toxicities (DLTs)
研究概览
简要总结
There're 2 parts in this interventional study:
- The goal of phase Ib trial is to evaluate the safety and tolerability of AK112 in combination therapies for the purpose of observing the incidence of dose limit toxicity (DLT) as well as the confirmation of maximum tolerable dose (MTD) in the treatment of advanced hepatocellular carcinoma (HCC), so as to determine the recommended phase 2 dose (RP2D) in the second part of the trial.
- The goal of phase II trial is to evaluate the safety and efficacy of AK112 in combination therapy or monotherapy in the treatment of HCC compared to the combination of Sintilimab and Bevacizumab biosimilar.
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
- None
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
- •Be able and willing to provide written informed consent.
- •Have a life expectancy of at least 3 months.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •HCC confirmed by histology/cytology or confirmed by the American Society for the Study of Hepatology (AASLD) clinical diagnostic criteria for hepatocellular carcinoma in patients with cirrhosis.
- •Barcelona Clinical Liver Cancer (BCLC) stage B or C.
- •Has failed standard treatment and has received no more than two lines of anti-tumor treatment in the past;
- •The BCLC staging is stage C, which is not suitable for curative and local treatment, or for stage B that cannot be cured after curative and/or local treatment.
- •Subjects who have not received any systematic anti-tumor treatment for HCC in the past.
- •According to RECIST v1.1, there is at least one untreatable measurable lesion, or a measurable lesion with clear imaging progression after local treatment, suitable for repeated and accurate measurement.
- •Liver function grading Child Pugh Grade A.
- •Has adequate organ function.
- •All subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
- •Able to to comply with all requirements of study participation (including all study procedures).
排除标准
- •Components confirmed by histology/cytology, such as fibrous layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
- •Except for HCC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other malignant tumors that have been cured through local treatment are not excluded, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ. If diagnosed with liver cancer or other malignant tumors more than 5 years before administration, pathological or cytological diagnosis of recurrent and metastatic lesions is required.
- •Tumor volume>50% liver volume; Portal vein cancer thrombus (Vp4), inferior vena cava cancer thrombus.
- •Tumors invade important organs and blood vessels around them, and researchers have determined that entering the study will cause a higher risk of bleeding.
- •There is central nervous system (CNS) metastasis, spinal cord compression, or meningeal metastasis.
- •There are pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
- •Previously received immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, and any other treatments targeting the immune mechanisms of tumors.
- •Received local treatment for the liver within 4 weeks prior to the first administration; Received palliative radiotherapy for non liver patients within 2 weeks prior to initial administration.
- •There is a history of non infectious pneumonia that requires systemic glucocorticoid treatment, or current lung diseases including but not limited to interstitial lung disease, pneumoconiosis, silicosis, drug-related pneumonia, and severely impaired lung function.
- •History of severe bleeding tendency or coagulation dysfunction.
- •Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia.
- •Any arterial or venous thromboembolism events, transient ischemic attacks, cerebrovascular accidents, hypertensive crises, or hypertensive encephalopathy occurred within 6 months prior to the first administration of medication.
- •Pregnant or lactating female subject.
- •Any prior or concurrent disease, treatment, or laboratory test abnormality that may confuse study results, affect subjects' full participation in the study, or may not be in their best interest to participate.
研究组 & 干预措施
Sintilimab in combination with Bevacizumab biosimilar
Active Comparator
干预措施: Sintilimab Injection (Drug)
AK112 in combination with AK130
Experimental
干预措施: AK112 (Drug)
AK112 in combination with AK130
Experimental
干预措施: AK130 (Drug)
AK112 in combination with AK127
Experimental
干预措施: AK112 (Drug)
AK112 in combination with AK127
Experimental
干预措施: AK127 (Drug)
AK112 in combination with Cadonilimab
Experimental
干预措施: AK112 (Drug)
AK112 in combination with Cadonilimab
Experimental
干预措施: Cadonilimab (Drug)
AK112
Experimental
干预措施: AK112 (Drug)
Sintilimab in combination with Bevacizumab biosimilar
Active Comparator
干预措施: Bevacizumab biosimilar (Drug)
结局指标
主要结局
Number of subjects with dose limiting toxicities (DLTs)
时间窗: During the first three weeks.
DLTs will be assessed during the first three weeks of treatment. DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT observation period.
Number of subjects with adverse events (AEs)
时间窗: From the time of informed consent signed through 90 days after the last dose of study drug.
AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.
Objective Response Rate (ORR) (Phase II)
时间窗: Up to approximately 2 years.
ORR is defined as the proportion of subjects with BOR response of CR or PR (based on RECIST Version 1.1).
次要结局
- Objective Response Rate (ORR) (Phase Ib)(Up to approximately 2 years.)
- Objective Response Rate (ORR) Per mRECIST(Up to approximately 2 years.)
- Disease control rate (DCR)(Up to approximately 2 years.)
- Duration of Response (DoR)(Up to approximately 2 years.)
- Progression Free Survival (PFS)(Up to approximately 2 years.)
- Time to response (TTR)(Up to approximately 2 years)
- Overall survival (OS)(From baseline until death due to any cause.)
研究者
研究点 (2)
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