A Multicenter, Open-label, Phase 1a/1b Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B3227 as Monotherapy and in Combination With Tislelizumab in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 23
- 主要终点
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a first-in-human (FIH), open-label, multicenter dose escalation and expansion study of BGB-B3227, a humanized immunoglobulin G1 (IgG1) antibody. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-B3227 as a monotherapy or in combination with tislelizumab with or without chemotherapy in participants with selected advanced or metastatic solid tumors. The study will also identify recommended dose(s) for expansion (RDFE[s]) of BGB-B3227 administered alone and in combination with tislelizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically confirmed locally advanced or metastatic solid tumors with a high prevalence of mucin-1 (MUC1) expression
- •At least 1 measurable lesion per RECIST v1.1
- •Stable Eastern Cooperative Oncology Group Performance Status of ≤ 1
- •Adequate organ function
- •Willing to use a highly effective method of birth control
排除标准
- •History of prior ≥ Grade 3 Cytokine Release Syndrome (CRS)
- •History of severe Infusion-Related Reactions (IRRs), allergic reactions, or hypersensitivity to any ingredients or components of the study treatments
- •Infection requiring systemic (oral or intravenous) therapy ≤ 14 days before the first dose of study drug(s), or participants with symptomatic COVID-19 infection
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •Active autoimmune disease or history of autoimmune disease(s) that may relapse
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1b: Dose Expansion
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.
干预措施: Chemotherapy (Drug)
Phase 1a Part A: Dose Escalation (BGB-B3227 Monotherapy)
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated as monotherapy.
干预措施: BGB-B3227 (Drug)
Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab)
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab.
干预措施: BGB-B3227 (Drug)
Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab)
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab.
干预措施: Tislelizumab (Drug)
Phase 1b: Dose Expansion
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.
干预措施: BGB-B3227 (Drug)
Phase 1b: Dose Expansion
Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From first dose of the study drug(s) to 30 days after the last dose or 90 days after last dose of tislelizumab, approximately 9 months
Number of participants with AEs and SAEs, including findings from physical examinations, laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined Adverse Event of Special Interest (AESI) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
时间窗: Approximately 9 months
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B3227
时间窗: Approximately 9 months
RDFE of BGB-B3227 alone or in combination with tislelizumab will be determined based upon the MTD or MAD.
Phase 1b: Objective Response Rate (ORR)
时间窗: From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months
ORR is defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-B3227
时间窗: Approximately 12 months
RP2D established from Phase 1a for BGB-B3227 for administration in combination with tislelizumab and chemotherapy in selected tumor types.
次要结局
- Phase 1a: ORR(From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 6 months)
- Phase 1b: Progression-Free Survival (PFS)(From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months)
- Phase 1b: Number of Participants with AEs and SAEs(From first dose of the study drug(s) to 30 days after the last dose, or 90 days after last dose of tislelizumab; approximately 12 months)
- Phase 1a and 1b: Disease Control Rate (DCR)(From first dose of study treatment drug(s) until confirmed response or stable disease; approximately 6 months for Phase 1a and 12 months for Phase 1b)
- Phase 1a and 1b: Duration of Response (DoR)(From confirmed response to disease progression or death; approximately 6 months for Phase 1a and 12 months for Phase 1b)
- Phase 1a and 1b: Serum Concentrations of BGB-B3227(From first dose of BGB-B3227 up to 30 days after last dose of BGB-B3227; approximately 6 months for Ph1a and 12 months for Ph1b)
- Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) against BGB-B3227(From first dose of BGB-B3227 up to 30 days after last dose of BGB-B3227; approximately 6 months for Phase 1a and 12 months for Phase 1b)
- Phase 1a: Area under the Curve (AUC) of BGB-B3227(Approximately 4 months)
- Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-B3227(Approximately 4 months)
- Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-B3227(Approximately 4 months)
- Phase 1a: Trough concentration (Ctrough) of BGB-B3227(Approximately 4 months)
- Phase 1a: Accumulation ratio of BGB-B3227(Approximately 4 months)
- Phase 1a: Terminal half-life (t1/2) of BGB-B3227(Approximately 4 months)