A Phase I, Open-Label, Multinational, Multicenter, Dose Escalation and Expansion Study of BH3120, as a Single Agent and in Combination With Pembrolizumab, in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 245
- 试验地点
- 10
- 主要终点
- Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
研究概览
简要总结
This is a First-in-Human, Phase 1, Dose-Escalation and Dose-Expansion study of BH3120, as a single agent and in combination with pembrolizumab, to assess safety, tolerability, MTD, RP2D, PK, and efficacy in patients with advanced or metastatic solid tumors. Dose-Escalation part is planned to establish the MTD or RD for Dose-Expansion part, while Dose-Expansion part is designed to assess potential efficacy of BH3120, as a single agent and in combination with pembrolizumab, when administered at the RD to subjects in indication-specific expansion cohorts.
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
- •Have a Histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy.
- •PD-L1 positive expression (Tumor Proportion Score ≥1% or Combined Positive Score ≥1).
- •Have at least one lesion, not previously irradiated that can be accurately measured per RECIST version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Age of 18 years or older (or country's legal age of majority if the legal age was >18 years)
- •Adequate Hematologic and liver function.
排除标准
- •Has received prior therapy with an anti-4-1BB(CD137) agent.
- •Known active CNS metastases and/or carcinomatous meningitis.
- •Known additional malignancy that is progressing or has required active treatment.
- •History of chronic liver disease or evidence of hepatic cirrhosis.
- •History of severe toxicities associated with a prior immunotherapy.
- •Has ongoing or suspected autoimmune disease.
- •Known active and clinically significant bacterial, fungal or viral infection including known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, immunocompromised patients.
研究组 & 干预措施
BH3120 + pembrolizumab
Arm B: BH3120 in combination with pembrolizumab
干预措施: BH3120 (Drug)
BH3120
Arm A: BH3120 Monotherapy
干预措施: BH3120 (Drug)
BH3120 + pembrolizumab
Arm B: BH3120 in combination with pembrolizumab
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
时间窗: Throughout the study until end of safety follow-up period (90 days after the last treatment)
To evaluate safety and tolerability of BH3120 as a single agent and in combination with pembrolizumab administration
Incidence and nature of DLTs
时间窗: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
To evaluate safety and tolerability of BH3120 as a single agent and in combination with pembrolizumab administration
次要结局
- The terminal half-life (T1/2)(Throughout the study until treatment discontinuation (up to 2-3 years))
- Frequency of anti-drug antibodies (ADA)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The maximum serum concentration (Cmax)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The time to reach Cmax (Tmax)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The AUC extrapolated to infinity (AUCinf)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The area under the concentration-time curve from time 0 to the last observable concentration (AUClast)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The AUC during the dosing interval (AUCtau)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The apparent volume of distribution (Vd/F)(Throughout the study until treatment discontinuation (up to 2-3 years))
- Objective response rate (ORR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- The apparent clearance (CL/F)(Throughout the study until treatment discontinuation (up to 2-3 years))
- Progression-free survival (PFS)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- Disease Control Rate (DCR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- Duration of response (DOR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))