A Multicenter, Open-Label, Phase 1a/b First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-C477 in Patients With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 310
- 试验地点
- 72
- 主要终点
- Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BG-C477 alone and in combination with anticancer agents in participants with selected advanced solid tumors.
详细描述
This new study will check how safe and helpful a potential anticancer drug called BG-C477 is. This drug will be tested by itself or combined with other anticancer agents. The purpose of this study is to test if BG-C477 is safe and if it works in people with your disease when it is given on its own and in combination with other anticancer agents.
Note: 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
- •Participants must sign the informed consent form (ICF) and be capable of giving written informed consent
- •Participants must consent to provide an archival tumor tissue sample or a fresh baseline biopsy
- •Phase 1a (Dose Escalation): Histologically confirmed advanced, metastatic, or unresectable solid tumors, that were previously treated with at least 2 lines of standard systemic therapy or for whom no standard treatment is available in the medical judgment of the investigator
- •Phase 1b (Dose Expansion) Part A: Histologically confirmed advanced or metastatic select solid tumors that were previously treated with and progressed from at least 1 line of standard systemic therapy
- •Phase 1b (Dose Expansion) Part B: Histologically confirmed advanced or metastatic select solid tumors who have previously received 0 or 1 line of systemic therapy for advanced disease
- •≥ 1 measurable lesion as assessed by RECIST v1.1
- •Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- •Adequate organ function
- •Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 8 months after the last dose of BG-C477, for ≥ 6 months after the last dose of chemotherapy, and for ≥ 4 months after the last dose of tislelizumab,whichever comes later
- •Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for ≥ 5 months after the last dose of BG-C477, for ≥ 3 months after chemotherapy, and for ≥ 4 months after the last dose of tislelizumab, whichever comes later.
排除标准
- •Prior treatment with any carcinoembryonic antigen (CEA)-targeted ADCs or ADCs containing topoisomerase 1 (TOP1) inhibitor as payload
- •History of severe allergic reactions, severe reaction to infusion, or hypersensitivity to the active ingredient and excipients of the study drug(s) or protein-based therapeutics
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •Any malignancy ≤ 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: BG-C477 Monotherapy Dose Escalation
Sequential cohorts of increasing dose levels of BG-C477 will be evaluated as monotherapy.
干预措施: BG-C477 (Drug)
Phase 1b Part B: Combination Therapy Expansion
Sequential cohorts of increasing dose levels of BG-C477 will be evaluated in combination with anticancer agents, including chemotherapy or tislelizumab.
干预措施: Chemotherapy (Drug)
Phase 1a: BG-C477 Monotherapy Safety Expansion
Selected dose levels that have been determined to be safe in Phase 1a dose escalation will be further evaluated in monotherapy.
干预措施: BG-C477 (Drug)
Phase 1b Part B: Combination Therapy Expansion
Sequential cohorts of increasing dose levels of BG-C477 will be evaluated in combination with anticancer agents, including chemotherapy or tislelizumab.
干预措施: Tislelizumab (Drug)
Phase 1b Part B: Combination Therapy Expansion
Sequential cohorts of increasing dose levels of BG-C477 will be evaluated in combination with anticancer agents, including chemotherapy or tislelizumab.
干预措施: BG-C477 (Drug)
Phase 1b Part A: BG-C477 Monotherapy Expansion and Dose Optimization
Participants with selected advanced solid tumors will be evaluated at different dose levels of RDFEs identified in Phase 1a.
干预措施: BG-C477 (Drug)
结局指标
主要结局
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
时间窗: Approximately 1 year
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 BG-C477
时间窗: Approximately 1 year
RDFE of BG-C477 monotherapy will be determined based upon available data.
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 (up to approximately 2 years)
Number of participants with AEs and SAEs, including findings from abnormal laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined Adverse Event of Clinical Interest (AECI) criteria.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BG-C477
时间窗: Approximately 2 years
RP2D of BG-C477 alone and in combination with anticancer agents will be determined based upon available data.
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 2 years
ORR is defined as the percentage of participants with 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.
次要结局
- Phase 1a: ORR(Approximately 1 year)
- Phase 1a and 1b: Duration of Response (DOR)(Approximately 2 years)
- Phase 1a and 1b: Disease Control Rate (DCR)(Approximately 2 years)
- Phase 1b: Progression-Free Survival (PFS)(Approximately 2 years)
- Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) against BG-C477(Approximately 2 years)
- Phase 1a and 1b: Apparent volume of distribution at steady state (Vss) of BG-C477(Approximately 2 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 (up to approximately 2 years))
- Phase 1a and 1b: Minimum concentration (Cmin) of BG-C477(Approximately 2 months)
- Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-C477 antibody-drug conjugate (ADC), BG-C477 total antibody, and free payload(Approximately 2 months)
- Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-C477(Approximately 2 months)
- Phase 1a and 1b: Area under the concentration-versus-time curve during dosing interval (AUCtau) of BG-C477(Approximately 2 months)
- Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-C477(Approximately 2 months)
- Phase 1a and 1b: Systemic clearance (CL/F) of BG-C477(Approximately 2 months)