An Exploratory Clinical Study to Evaluate the Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of BC006 Monoclonal Antibody Injection in Patients With Advanced Solid Tumors Including Giant Cell Tumor of Tendon Sheath
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This is a first in human, open-label, exploratory phase I clinical study including dose escalation (Ia) and dose expansion (Ib) stage. It aims to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BC006 in giant cell tumor of tendon sheath (GCTTS) and other advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form.
- •Age ≥ 18 years.
- •Clinical diagnosis:
- •Dose Escalation: Phase Ia
- •Histologically or cytologically confirmed GCTTS: initial treatment unresectable, or postoperative recurrence unresectable, or refuse surgical treatment.
- •Patients with histologically or cytologically confirmed advanced solid tumor, who have progression after prior SOC therapy, or who intolerant to SOC, or for whom there is no SOC therapy available.
- •Dose Expansion: Phase Ib
- •Cohort 1: Histologically or cytologically confirmed GCTTS: initial treatment unresectable, or postoperative recurrence unresectable, or refuse surgical treatment.
- •Cohort 2~4: Patients with histologically or cytologically confirmed advanced solid tumor which is sensitive to Ia treatment，who have progression after prior SOC therapy, or who intolerant to SOC, or for whom there is no SOC therapy available.
- •Life expectancy ≥ 12 weeks.
- •Ia: at least one evaluable lesion; Ib: at least one measureable lesion as defined by RECIST V1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Evidence of adequate organ function by standard laboratory tests:
- •Adequate hematological function: Hemoglobin (Hgb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, Platelets (Plts) ≥ 90 × 109/L.
- •Adequate liver function: Total bilirubin ≤ 1.5 × the upper limit of normal (ULN), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) ≤ 2.5 × ULN (AST≤ 5 × ULN, ALT≤ 5 × ULN for subjects with liver metastases).
- •Adequate renal function: Creatinine ≤ 1.5 × ULN, or Creatinine clearance by Cockcroft Gault formula ≥ 50 mL/min.
- •Adequate Coagulation function: Activated partial thrombin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN, international standardized ratio (INR) ≤ 1.5 × ULN.
- •Female patients of child-bearing potential or male patients with a female partner(s) of child-bearing potential must agree to use reliable contraceptive methods (hormonal, condoms or abstinence) for the duration of the study and for 6 months after the last dose of BC006; women of child-bearing potential must have a negative blood or urine pregnancy test within 7 days prior to enrollment.
排除标准
- •Prior anti-tumor therapies such as radiotherapy, chemotherapy, targeted therapy, endocrine therapy, immunotherapy or other investigational agents within 4 weeks before the first dose of BC
- •Prior treatment with any anti-CSF-1R inhibitor.
- •Any toxicity from previous anti-tumor treatments have not recovered to CTCAE V5.0 grade ≤ 1 (except treatment-related alopecia).
- •Patients with untreated or clinically symptomatic brain metastases, spinal cord compression, cancerous meningitis, or patients with evidence that brain and spinal cord metastases have not been controlled (Patients with previously treated brain metastases may participate provided they are clinically and imaging stable for at least 4 weeks prior to first dose of BC006, have no evidence of cerebral edema and are off steroids).
- •Patients with severe cardiovascular diseases: cardiac arrhythmia requiring clinical intervention; acute coronary syndrome, congestive heart failure, stroke or other ≥ grade 3 cardiovascular events within 6 months; New York Heart Association (NYHA) cardiac function ≥ grade II or left ventricular ejection fraction (LVEF) <50%; poorly controlled hypertension as judged by the investigator are not suitable to participate in the study.
- •Receipt of a live vaccine within 4 weeks prior to the first dose of BC006 or anticipation that such a live vaccine will be required during the study.
- •Patients with symptomatic pleural, abdominal, or pericardial effusions that require repeated puncture and drainage treatment and cannot be relieved; patients with stable disease after receiving treatment (including therapeutic thoracentesis or abdominal puncture) are allowed to enroll.
- •In the opinion of the investigator, patients have any clinical or laboratory examination abnormality or other conditions that are not suitable to participate in the study.
研究组 & 干预措施
Dose Escalation: Phase Ia
Participants will receive escalating doses of BC006 at assigned dose (0.08, 0.3, 1.0, 3.0, 10, 20 mg/kg) via intravenous (IV) infusion every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 48 weeks of treatment, whichever occurs first.
干预措施: BC006 (Drug)
Dose Expansion: Phase Ib Cohort 1
Participants with GCTTS will receive BC006 at recommended dose for expansion (RDE) IV every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 24 weeks of treatment, whichever occurs first.
干预措施: BC006 (Drug)
Dose Expansion: Phase Ib Cohort 2~4
Participants with other solid tumors will receive BC006 at RDE IV every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 48 weeks of treatment, whichever occurs first.
干预措施: BC006 (Drug)
结局指标
主要结局
Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
时间窗: Up to 28 days
Dose Escalation: Phase Ia
Maximum Tolerated Dose (MTD) of BC006
时间窗: Up to 28 days
Dose Escalation: Phase Ia
Recommended Dose for Expansion (RDE) of BC006
时间窗: Through study completion, an average of 1 year
Dose Escalation: Phase Ia
Number of Participants with TEAEs
时间窗: Through study completion, an average of 1 year
Graded according to the NCI CTCAE V5.0
Number of Participants with SAEs
时间窗: Through study completion, an average of 1 year
Graded according to the NCI CTCAE V5.0
次要结局
- Tmax(From first dose of BC006, an average of 6 months)
- Number of Participants with Anti-BC006 Antibodies (ADAs)(From first dose of BC006, an average of 6 months)
- Objective Response Rate (ORR)(From first dose of BC006, up to 2 years)
- Disease Control Rate (DCR)(From first dose of BC006, up to 2 years)
- Progression-Free Survival (PFS)(From first dose of BC006, up to 2 years)
- Duration of Response (DOR)(From first dose of BC006, up to 2 years)
- Cmax(From first dose of BC006, an average of 6 months)
- AUC0-t(From first dose of BC006, an average of 6 months)
- Pharmacodynamic (PD) Parameters(From first dose of BC006, an average of 6 months)
- t1/2(From first dose of BC006, an average of 6 months)