Phase 1/2, Open-Label, Multicenter, Dose Escalation and Expansion Study of BHB810 in Participants With Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs) per Common Terminology Criteria for Adverse Events v6.0 (CTCAE v6.0)
研究概览
简要总结
This study is looking at how safe BHB810 is in adults with gastric and gastroesophageal adenocarcinoma (GEJ). The purpose of this study is also to look at: how well the study drug works, how the study drug moves into, through, and out of the body, and how your body reacts to the study drug. Participants will get an IV infusion of BHB810 every 2 weeks while on study treatment.
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
- •Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
- •Histologically confirmed advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has progressed on, was nonresponsive to, or for which no standard or available curative therapy exists.
- •Participants in Phase 1 Backfill Cohorts & Phase 2 must be CDH17-positive by central testing.
- •Other gastrointestinal (GI) tumor types may be enrolled in Backfill Cohorts and Phase
- •At least 1 measurable target lesion at baseline per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
- •Provision of FFPE archival tumor tissue. Additional fresh biopsies at screening are required in Phase 1 Backfill Cohorts and Phase
- •Adequate organ and marrow function as defined in the protocol
排除标准
- •Prior cancer treatment as follows, relative to the first planned dose of trial intervention:
- •Chemotherapy or targeted therapy withing 4 weeks or 5-halflives (whichever is shorter)
- •Monoclonal antibody-based therapy (including ADCs) within 4 weeks
- •Immune checkpoint inhibitors within 4 weeks
- •Wide-field radiation therapy (>30% marrow-bearing bones) within 4 weeks or < 2 weeks of focal palliative radiation to nontarget lesions
- •Prior treatment with a CDH17-directed therapy or an ADC with an auristatin (MMAE or MMAF)
- •Known hypersensitivity or allergic reaction to BHB810 or it's excipients
- •Left ventricular ejection fraction <50% or history of congestive heart failure Class III/IV
- •QTc interval > 470 msec, history of risk factors for Torsade de Pointes, or taking a medication known to prolong QT/QTc
- •Pregnant or breastfeeding females, or if you or your partner are planning to become pregnant
- •Known or suspected brain metastases, leptomeningeal disease, or spinal cord compression. Participants with stable, treated brain metastases may be enrolled.
- •Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or CYP3A4 sensitive substrate within 2 weeks of first dose of trial intervention
- •Any condition that may compromise participant safety, compliance, or interfere with the evaluation of the study drug.
研究组 & 干预措施
Recommended Phase 2 Dose Level 1 (RP2D1)
Dose level 1 of 2 prospective recommended phase 2 dose levels
干预措施: BHB810 (Drug)
Recommended Phase 2 Dose Level 2 (RP2D2)
Dose level 2 of 2 prospective recommended phase 2 dose levels
干预措施: BHB810 (Drug)
Dose Escalation and Backfill Cohorts
Dose escalation and backfill cohorts
干预措施: BHB810 (Drug)
结局指标
主要结局
Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs) per Common Terminology Criteria for Adverse Events v6.0 (CTCAE v6.0)
时间窗: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months
Investigate the safety and tolerability of BHB810 by evaluation of AEs, SAEs, DLTs, and clinically significant changes safety assessments, like lab tests, vital signs, and other safety assessments Phase 1 (Dose Escalation \& Backfill Cohorts) and Phase 2 (Dose Optimization) DLTs apply to Phase 1 Dose Escalation Cohorts only.
Incidence of participants who have a dose modification of BHB810 due to toxicity
时间窗: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months
Investigate the safety and tolerability of BHB810 by assessment of dose modifications due to toxicity Phase 1 (Dose Escalation \& Backfill Cohorts)
Overall Response Rate (ORR)
时间窗: Screening through End of Treatment, an average of 6 months
Identify the recommended Phase 2 dose (RP2D) by comparing 2 doses of BHB810 by evaluating the ORR of participants according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Phase 2 (Dose Optimization)
次要结局
- Clinical Benefit Rate (CBR)(Screening through End of Treatment, an average of 6 months)
- Duration of Response (DOR)(Screening through End of Treatment or last scan, an average of 6 months)
- Progression Free Survival (PFS)(Screening through End of Treatment, an average of 6 months)
- Overall Survival (OS)(Screening through End of Study, an average of 10 months)
- Pharmacokinetics (PK): PK Analytes(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Area under the concentration-time curve (AUC)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Area under the concentration-time curve from zero to the end of a dosing interval at steady-state (AUC0-tau)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Maximum concentration of BHB810 (Cmax) Phase 1 (Dose Escalation & Backfill Cohorts) Phase 2 (Dose Optimization)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Time to reach maximum drug concentration of BHB810 (Tmax)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Area under the concentration-time curve from zero to infinity (AUC0-inf)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Terminal elimination half-life (t1/2)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Volume of drug distribution during terminal phase (Vz)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Total body clearance of the drug (CL)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Pharmacokinetics: Area under the concentration-time curve from zero to last measurable concentration sample time (AUC0-last)(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)
- Incidence of antidrug antibodies (ADAs) in blood before and after BHB810 administration(At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months)