A Phase I, Open-label, Dose-Escalation and Dose-expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Efficacy of HC006 in Advanced Solid Tumor Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Number of participants with Serious adverse events(SAEs)as assessed by CTCAE v5.0
研究概览
简要总结
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), Immunogenicity and preliminary antitumor activity of HC006 in subjects with advanced solid tumor malignancies. This study is a first-in-human (FIH) study of HC006 in subjects with advanced solid tumors.
详细描述
HC006, a novel therapeutic monoclonal antibody that specifically binds to human C-C motif chemokine receptor 8 (CCR8) and is designed to selectively deplete tumor-infiltrating T regulatory cells (Tregs) with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). In mouse tumor models, HC006 has demonstrated excellent antitumor activity and safety profile. This first-in-human (FIH) study will be conducted in two parts. In the Dose-Escalation part, testing will be done on up to 31 subjects to determine the maximum tolerated dose (MTD) and the recommended dose (RD). In the Dose-expansion part, we will evaluate the safety and efficacy of the recommended dose of HC006 in the treatment of advanced solid tumor subjects without standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically confirmed and documented diagnosis of locally advanced unresectable or metastatic advanced solid tumor that is refractory to standard treatment, or intolerant to standard treatment, or for which no standard treatment exists.
- •At least one measurable disease for expansion cohorts per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1(dose escalation only requires at least one assessable lesion)
- •Agree to provide archived or fresh tumor tissue samples of primary or metastatic lesions for expansion cohorts.
- •Life expectancy ≥12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Have adequate organ function as described in the protocol.
- •Agree to adopt effective contraceptive measures.
排除标准
- •Prior exposure to CCR8 inhibitor or hypersensitivity to any ingredient of the study drug.
- •Treatment with any systemic anti-cancer treatment within 4 weeks before first dose of study drug.
- •Use of any live attenuated vaccines within 28 days.
- •With primary central nervous system (CNS) tumors or unstable CNS metastases.
- •Have active or history of autoimmune disease or immunodeficiency disease.
- •With active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
- •With any mental or cognitive impairment that may limit their understanding, implementation.
- •Major surgery within 4 weeks of study drug administration.
- •Have uncontrolled or severe illness, including but not limited to severe cardiovascular disease, interstitial lung disease or non-infectious pneumonia, or uncontrollable clinical third luminal effusion.
- •Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.
- •History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma.
- •Women who are pregnant or breastfeeding.
- •Other protocol defined exclusion criteria may apply.
研究组 & 干预措施
HC006 Dose Escalation
干预措施: HC006 (Drug)
HC006 Dose Expansion
干预措施: HC006 (Drug)
结局指标
主要结局
Number of participants with Serious adverse events(SAEs)as assessed by CTCAE v5.0
时间窗: up to 24 months
Incidence of Serious adverse events(SAEs)
Number of participants with Dose Limiting Toxicities(DLTs)as assessed by protocol
时间窗: up to 24 months
Incidence of Dose Limiting Toxicities(DLTs)
Number of participants with adverse events(AEs) as assessed by CTCAE v5.0
时间窗: up to 24 months
Incidence of adverse events(AEs)
Percentage of Participants Experiencing Laboratory and ECG Abnormalities According to the NCI CTCAE v5.0
时间窗: up to 24 months
Percentage of Participants Experiencing Laboratory and ECG Abnormalities According to the NCI CTCAE v5.0
次要结局
- Overall Survival (OS)(up to 24 months)
- Duration of response (DOR) per RECIST 1.1(up to 24 months)
- Pharmacokinetic (PK) Parameter:Maximum serum concentration (Cmax)(up to 24 months)
- Disease Control Rate (DCR) per RECIST 1.1(up to 24 months)
- Time To Response (TTR) per RECIST 1.1(up to 24 months)
- progression-Free Survival (PFS) per RECIST 1.1(up to 24 months)
- PK Parameter:Area Under the Concentration-time Curve (AUC)(up to 24 months)
- Objective Response Rate (ORR) per RECIST 1.1(up to 24 months)
- PK Parameter:Time to reach Cmax (Tmax)(up to 24 months)
- Immunogenicity(up to 24 months)
- Time to progression (TTP) per RECIST 1.1(up to 24 months)