A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-A3055, Alone and in Combination With Tislelizumab in Patients With Selected Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 99
- 试验地点
- 26
- 主要终点
- Phase 1a: Number of participants with adverse events (AEs)
研究概览
简要总结
This study aims to evaluate how safe and well-tolerated the treatment is, how the body processes it, how it works on the tumors, and whether it shows early signs of fighting cancer in people with certain advanced or metastatic solid tumors.
Key details of the study include:
- The study is expected to last about 36 months.
- Participants will receive treatment until they either no longer benefit from the treatment, experience side effects that are too severe, or choose to stop participating.
详细描述
The primary objective of the study is to assess the safety and tolerability of BGB-A3055 alone or in combination with Tislelizumab during dose escalation and to determine the recommended dose for expansion. During dose expansion, the primary objective will be to assess preliminary anti-tumor activity and further characterize the safety of the recommended dose for expansion.
. Around 318 participants will be enrolled in this study, and they will be assigned to different treatment groups. Both the participants and their doctors will be aware of which treatment group they are assigned to throughout the study.
The treatments, BGB-A3055 alone or in combination with Tislelizumab, will be administered intravenously to evaluate their safety and determine the highest dose that can be tolerated by participants. The study will be conducted at multiple medical centers worldwide. The expected duration of participation in this study is two years. Treatment will continue until participants no longer receive any benefits from the drugs, experience excessive side effects, or decide to withdraw their consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Age≥18 years on the day of signing the informed consent form (ICF) (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older).
- •All participants are also required to demonstrate an ECOG Performance Status score of ≤1 within 3 days before the first dose of study drug(s) and have adequate organ function.
- •Participants with histologically confirmed advanced or metastatic solid tumors associated with high CCR8 and who have previously received adequate available standard systemic therapy or for whom treatment is not available or not tolerated and who have not received any prior therapy targeting CCR
- •>=1 Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Participants should be able to provide archival tumor tissue samples (as block or unstained slides) or fresh biopsy if there is no archival tissue at baseline. For selected cohorts, participants should be willing to provide post-treatment fresh biopsy at specified timepoints.
- •Females of childbearing potential and nonsterile males must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 120 days after the last dose of BGB-A3055 or tislelizumab (whichever is later), or up to 9 months after the last dose of chemotherapy, whichever is later. Females of childbearing potential must also have a negative urine or serum pregnancy test result ≤ 7 days before the first dose of study drug(s).
排除标准
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Active autoimmune diseases or history of autoimmune diseases that may relapse
- •Any malignancy ≤ 3 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 with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
- •Participants with hepatitis B infection with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL). Participants with active hepatitis C, and participants with HIV infection.
- •Note: Participants with chronic hepatitis B infection or resolved hepatitis B infection (HBV DNA < 500 IU/mL or < 2500 copies/mL) and considered stable are eligible. Participants with a negative HCV antibody test result at screening or a positive HCV antibody test result followed by a negative HCV RNA test result at screening are eligible to participate. Participants with treated HIV infection may be included if certain criteria are met.
- •History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.
- •Grade 3 immune-mediated adverse events on prior immune-oncology agent.
- •Cardiovascular risk factors, including but not limited to pulmonary embolism ≤ 28 days or history of acute myocardial infarction or heart failure ≤ 6 months before the first dose of study drug(s).
- •Uncontrolled diabetes.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a Part A: Dose Escalation (BGB-A3055 Monotherapy)
Different groups of participants will receive increasing doses of BGB-A3055 alone to determine the most appropriate dosage levels.
干预措施: BGB-A3055 (Drug)
Phase 1a Part B: Dose Escalation (BGB-A3055 + tislelizumab)
Different groups of participants will receive increasing doses of BGB-A3055 in combination with tislelizumab to determine the most appropriate dosage levels.
干预措施: BGB-A3055 (Drug)
Phase 1a Part B: Dose Escalation (BGB-A3055 + tislelizumab)
Different groups of participants will receive increasing doses of BGB-A3055 in combination with tislelizumab to determine the most appropriate dosage levels.
干预措施: Tislelizumab (Drug)
Phase 1b (Dose Expansion):
Participants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
干预措施: BGB-A3055 (Drug)
Phase 1b (Dose Expansion):
Participants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
干预措施: Tislelizumab (Drug)
Phase 1b (Dose Expansion):
Participants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Phase 1a: Number of participants with adverse events (AEs)
时间窗: Up to 2 Years
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and the American Society for Transplantation and Cellular Therapy \[ASTCT\] consensus grading system for cytokine release syndrome \[CRS\]), and including findings from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1a: Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BGB-A3055
时间窗: Up to 2 Years
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate of 30%. MAD is defined as the highest dose administered.
Phase 1a: Recommended dose for expansion (RDFE) of BGB-A3055 alone or in combination with tislelizumab
时间窗: Up to 2 Years
The RDFEs of BGB-A3055, alone or in combination with tislelizumab will be determined based on biological effectiveness taking preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration.
Phase 1b (Dose Expansion): Objective Response Rate (ORR)
时间窗: Up to 2 Years
ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Serum concentration of BGB-A3055 at specified time points(Up to 2 Years)
- Phase 1b: Progression-Free Survival (PFS)(Up to 2 Years)
- Phase 1b: Number of participants with adverse events (AEs)(Up to 2 Years)
- Phase 1b: Association of CCR8 expression with clinical efficacy(Up to 2 Years)
- Phase 1b: Association of PD-L1 expression with clinical efficacy(Up to 2 Years)
- Phase 1a: ORR(Up to 2 Years)
- Time to Response (TTR)(Up to 2 Years)
- Duration of Response (DOR)(Up to 2 Years)
- Disease Control Rate (DCR)(Up to 2 Years)
- Clinical Benefit Rate (CBR)(Up to 2 Years)
- Number of participants with anti-drug antibodies (ADAs) against BGB-A3055(Up to 2 Years)