A Phase 1, Open-label, Multicenter, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HCB301 in Subjects With Advanced Solid Tumors or Relapsed and Refractory cHL
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 7
- 主要终点
- Number/incidence and percentage of subjects with adverse events, including ADA.
研究概览
简要总结
The purpose of this study is to find out whether IV injection of HCB301 is an effective treatment for different types of advanced solid tumors and relapsed and refractory classical Hodgkin lymphomas and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
详细描述
This is a phase 1, open-label, multicenter, dose-escalation study. This study is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and identification of maximum tolerated dose (MTD) of HCB301 intravenous injection in adults with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
Eligible subjects must have failed standard therapies, been intolerable, or been considered medically inappropriate by the investigator. Subjects will be treated until unacceptable AEs, radiographic or clinical documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study, whichever occurs first.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and be willing to sign the ICF.
- •Male and female subjects of ≥18 years of age.
- •Histologically/cytologically confirmed, locally advanced solid tumor:
- •subjects confirmed advanced solid tumors who have relapsed or refractory and should have no options for standard or approved therapies known to potentially confer clinical benefit or classical Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of systemic therapy.
- •For subjects with advanced solid tumors - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
- •For subjects with classical Hodgkin lymphoma - must have classical Hodgkin lymphoma that is measurable or assessable for response.
- •Must have ECOG performance status of 0 to 1 at Screening.
- •Able to provide tumor tissue samples.
- •Have a life expectancy of ≥12 weeks.
排除标准
- •With known history of hypersensitivity to any components of HCB
- •Known active or untreated CNS metastases and/or carcinomatous meningitis.
- •Have undergone a major surgery or radical radiotherapy within 28 days or palliative radiotherapy within 14 days or have used a radioactive drug within 56 days prior to the first dose of HCB
- •Clinically significant cardiovascular condition.
- •Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
- •With known inherited or acquired bleeding disorder or bleeding diathesis. .
- •Have RBC transfusion within 4 weeks prior to Screening.
- •With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
- •Any investigational or approved systemic cancer therapy administered within 21 days or 5 half-lives, whichever is shorter, before the first dose of the study drug.
- •Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 100 mg/QD.
- •Have used herbal medication within 14 days prior to the first dose of HCB
- •Have received any treatment targeting the SIRPα-CD47, PD-L1, or TGF-β pathway.
- •Have other malignancies requiring treatment within 2 years prior to the first dose of HCB
- •An investigational device used within 28 days prior to the first dose of HCB
- •Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
- •Known to have a history of alcoholism or drug abuse.
研究组 & 干预措施
Experimental: 0.3 mg/kg HCB301
0.3 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 0.6 mg/kg HCB301
0.6 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 1.2 mg/kg HCB301
1.2 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 4.8 mg/kg HCB301
4.8 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 2.4 mg/kg HCB301
2.4 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 9.6 mg/kg HCB301
9.6 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
Experimental: 15.0 mg/kg HCB301
15.0 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.
干预措施: HCB301 (Drug)
结局指标
主要结局
Number/incidence and percentage of subjects with adverse events, including ADA.
时间窗: 12 months
To evaluate the safety and tolerability of HCB301.
Number of subjects with MTD and RDE of HCB301.
时间窗: 12 months
To determine the MTD and RDE.
次要结局
- Disease Control Rate (DCR)(12 months)
- Duration of Response (DoR)(12 months)
- Time to maximum drug concentration in plasma (Tmax) of HCB301(12 months)
- Peak Plasma Concentration (Cmax) of HCB301(12 months)
- Terminal elimination half-life (t1/2) of HCB301(12 months)
- Overall Rate Response (ORR)(12 months)
- Progression-Free Survival (PFS)(12 months)
- Area under the plasma concentration versus time curve (AUC) of HCB301(12 months)