A Phase 1, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B455 in Patients With Selected 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
- 90
- 试验地点
- 14
- 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
The goal of this clinical trial is to learn if BGB-B455 can treat advanced or metastatic solid tumors expressing claudin 6 (CLDN6), a protein that is found on some tumors.
The main questions it aims to answer are:
- What is the recommended dosing for BGB-B455?
- What medical problems do participants have when taking BGB-B455?
The study has two parts:
- Phase 1a: dose escalation and safety expansion
- Phase 1b: dose expansion
详细描述
Claudin proteins are cell proteins that can play an important role in how cancer starts and progresses. Because of its preferential expression in tumors compared to normal tissues, CLDN6 is an ideal tumor antigen to target for treatment. BGB-B455 is a bispecific antibody (BsAbs) that targets CLDN6 on tumor cells and the CD3 receptor on T cells, which may provide a CLDN6-dependent antitumor immune response in a more tolerable manner without undue systemic toxicity.
This new study will check how safe and helpful this potential anticancer drug is. In addition, this study will explore the recommended dosing level for BGB-B455. This drug will be tested by itself or in combination with investigator-selected chemotherapy in participants with selected solid tumors expressing the CLDN6 protein.
This study is an open label study, meaning that both you and your study doctor will know what study drug/treatment you are given. This study has two parts:
- Phase 1a consists of a dose escalation part where increasing amounts of the study treatment are given to different dose cohorts, and a safety expansion part that will enroll additional participants at selected doses for further assessments.
- Phase 1b (dose expansion) will enroll participants at the best dose found in Phase 1a to see if it helps people with certain solid tumors.
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
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
- •Histologically or cytologically confirmed advanced or metastatic, and unresectable solid tumors who have previously received standard systemic therapy for advanced or metastatic disease or for whom treatment is not available or not tolerated. Only participants with CLDN6+ high-grade OC (ie, ovarian cancer, fallopian tube cancer, or primary peritoneal cancer) will be enrolled in dose escalation cohorts, starting from Protocol Amendment 3.
- •Agreement for collection of formalin-fixed paraffin-embedded (FFPE) tumor tissue for central CLDN6 testing and other biomarker assessments.
- •Tumor CLDN6 expression (CDLN6+) by central immunohistochemistry testing is required for certain cohorts.
- •≥ 1 measurable lesion as assessed by RECIST v1.
- •Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate organ function.
排除标准
- •Prior systemic anticancer therapy, including chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin), targeted therapy, and antibody drug conjugates (ADCs) that are standard or investigational agents (including herbal medicine or Chinese [or other country] patent medicines, ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug(s).
- •Palliative radiation treatment or other locoregional therapies ≤ 14 days before the first dose of study drug(s).
- •Live vaccine ≤ 28 days before the first dose of study drug(s). Vaccines for COVID-19 are allowed except for any live vaccine that may become available. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
- •Any major surgical procedure ≤ 28 days before the first dose of study drug(s).
- •History of prior ≥ Grade 3 cytokine release syndrome (CRS).
- •Participants with toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Dose Escalation and Safety Expansion
Sequential cohorts of increasing dose levels of BGB-B455 will be evaluated as monotherapy.
干预措施: BGB-B455 (Drug)
Phase 1b: Dose Expansion
Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B455 determined from Phase 1a as monotherapy or in combination with investigator-selected chemotherapy will be evaluated for selected indications based on emerging data.
干预措施: Chemotherapy (Drug)
Phase 1b: Dose Expansion
Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B455 determined from Phase 1a as monotherapy or in combination with investigator-selected chemotherapy will be evaluated for selected indications based on emerging data.
干预措施: BGB-B455 (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 the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months
Number of participants with AEs and SAEs, including laboratory abnormalities, and AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined adverse events of special interest (AESI) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B455
时间窗: Approximately 1 month
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: RDFE of BGB-B455
时间窗: Approximately 1 month
RDFE of BGB-B455 will be determined based upon the MTD or MAD.
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 18 months
ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined from tumor assessments by investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR and PR must be confirmed by repeat assessments.
次要结局
- Phase 1a: ORR(Approximately 18 months)
- Phase 1a and 1b: Duration of Response (DOR)(Approximately 18 months)
- Phase 1a and 1b: Disease Control Rate (DCR)(Approximately 18 months)
- Phase 1a and 1b: Time to Response (TTR)(Approximately 18 months)
- Phase 1a and 1b: Serum concentrations of BGB-B455(Approximately 7 months)
- Phase 1b: Progression-Free Survival (PFS)(Approximately 18 months)
- Phase 1b: Number of participants with AEs(From the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months)
- Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Trough Concentration (Ctrough) of BGB-B455(Approximately 7 months)
- Phase 1a and 1b: Apparent clearance (CL) of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Volume of distribution (Vd) of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Accumulation Ratio of BGB-B455(Approximately 4 months)
- Phase 1a and 1b: Terminal half-life (t1/2) of BGB-B455(Approximately 4 months)