A Phase 1/2 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants 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
- 630
- 试验地点
- 59
- 主要终点
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of BGB-B2033 alone or in combination with tislelizumab, with or without bevacizumab, in adults with advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors, non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC). The study will also determine the recommended Phase 2 dose (RP2D) of BGB-B2033 when given alone or in combination with tislelizumab and bevacizumab. The main questions it aims to answer are:
- Is BGB-B2033 safe and tolerable when given alone or in combination with tislelizumab, with or without bevacizumab?
- How does the body process BGB-B2033, and what are its effects on the body?
- Does BGB-B2033 show preliminary antitumor activity in participants with advanced or metastatic cancer?
Researchers will evaluate different doses and treatment combinations to determine the safest and most appropriate dose of BGB-B2033 for further study.
Participants will:
- Receive BGB-B2033 by intravenous infusion, either alone or in combination with tislelizumab, with or without bevacizumab.
- Have regular assessments to monitor safety, side effects, how their body processes and responds to BGB-B2033, and whether their cancer responds to treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 have one of the following unresectable, locally advanced, or metastatic tumor types:
- •Hepatocellular carcinoma (HCC): Histologically or cytologically confirmed HCC that is either Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC Stage B that is not amenable to, or has progressed after, loco-regional therapy and is not eligible for a curative treatment approach.
- •Alpha-fetoprotein (AFP)-producing gastric cancer (GC): Histologically confirmed GC with AFP > 20 ng/mL in blood or tumor tissue positive for AFP by a validated immunohistochemistry (IHC) assay based on local or central testing.
- •Germ cell tumors: Histologically confirmed germ cell tumors including extragonadal yolk sac tumors (e.g., located in the mediastinum, vagina, brain, retroperitoneum), and non-dysgerminomas for which no further curative systemic treatment options exist.
- •Glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC): Histologically confirmed GPC3-positive squamous NSCLC with prior exposure to a checkpoint inhibitor (CPI).
- •At least one evaluable lesion for dose escalation, and at least one measurable lesion for safety expansion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Adequate organ function as defined in the protocol.
- •Provision of tumor tissue samples is required for specified parts of the study.
排除标准
- •Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137).
- •Active leptomeningeal disease or uncontrolled/untreated brain metastases.
- •Active autoimmune disease or a history of autoimmune disease with potential for relapse.
- •Any malignancy diagnosed ≤ 2 years before the first dose of study drug(s), except: The cancer type under investigation in this study, or Locally recurring malignancies previously treated with curative intent.
- •Requirement for systemic corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days prior to the first dose of study drug(s).
- •Certain comorbidities involving the lungs, heart, bleeding conditions, or active infections, as defined in the protocol.
- •Note: Additional protocol-defined inclusion and exclusion criteria may apply.
研究组 & 干预措施
Part A (Monotherapy Dose Escalation and Safety Expansion)
Participants will receive ascending dose levels of BGB-B2033 monotherapy
干预措施: BGB-B2033 (Drug)
Part E (Monotherapy Dose Expansion in HCC)
Participants with HCC will receive BGB-B2033 as monotherapy.
干预措施: BGB-B2033 (Drug)
Part B (Triplet Dose Escalation)
Participants will receive BGB-B2033 in combination with tislelizumab and bevacizumab to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDFE) of the combination.
干预措施: BGB-B2033 (Drug)
Part B (Triplet and Doublet Safety Expansion)
Safety expansion arm for each combination therapy cohort (triplet and doublet)
干预措施: BGB-B2033 (Drug)
Part B (Triplet Dose Escalation)
Participants will receive BGB-B2033 in combination with tislelizumab and bevacizumab to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDFE) of the combination.
干预措施: Bevacizumab (Drug)
Part B (Doublet Run-in)
Participants will receive BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation.
干预措施: Tislelizumab (Drug)
Part B (Doublet Run-in)
Participants will receive BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation.
干预措施: BGB-B2033 (Drug)
Part B (Triplet and Doublet Safety Expansion)
Safety expansion arm for each combination therapy cohort (triplet and doublet)
干预措施: Tislelizumab (Drug)
Part B (Triplet and Doublet Safety Expansion)
Safety expansion arm for each combination therapy cohort (triplet and doublet)
干预措施: Bevacizumab (Drug)
Part C (Asia Monotherapy Dose Expansion in HCC)
Participants in Asian countries with HCC will receive BGB-B2033 as monotherapy.
干预措施: BGB-B2033 (Drug)
Part B (Triplet Dose Escalation)
Participants will receive BGB-B2033 in combination with tislelizumab and bevacizumab to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDFE) of the combination.
干预措施: Tislelizumab (Drug)
Part D (US Monotherapy Dose Expansion in HCC)
Participants in the United States (US) with HCC will receive BGB-B2033 as monotherapy.
干预措施: BGB-B2033 (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0/American Society for Transplantation and Cellular Therapy \[ASTCT\] for cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria;
Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033
时间窗: Up to approximately 2 years
The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.
Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC)
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0/American Society for Transplantation and Cellular Therapy \[ASTCT\] for cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria;
Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033
时间窗: Up to approximately 2 years
The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.
Recommended Phase 2 dose (RP2D) of BGB-B2033
时间窗: Up to approximately 2 years
The RP2D(s) will be determined based on a biologically effective dose by taking the totality of available preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration
次要结局
- Overall Response Rate (ORR)(Up to approximately 2 years)
- Duration of Response (DOR)(Up to approximately 2 years)
- Disease Control Rate (DCR)(Up to approximately 2 years)
- Progression Free Survival (PFS)(Up to approximately 2 years)
- Number of participants with anti-drug antibodies (ADAs) to BGB-B2033(Up to approximately 2 years)
- Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Investigator(Up to approximately 2 years)
- Parts C, D, and E: Duration of Response (DOR) as assessed by the investigator and IRC(Up to approximately 2 years)
- Parts C, D, and E: Progression Free Survival (PFS) as assessed by the investigator and IRC(Up to approximately 2 years)
- All Parts: Overall Survival (OS)(Up to approximately 2 years)
- Parts C, D, and E: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 2 years)
- Overall Response Rate (ORR)(Up to approximately 2 years)
- Duration of Response (DOR)(Up to approximately 2 years)
- Disease Control Rate (DCR)(Up to approximately 2 years)
- Progression Free Survival (PFS)(Up to approximately 2 years)
- Serum concentration of of BGB-B2033(Up to approximately 2 years)
- Number of participants with anti-drug antibodies (ADAs) to BGB-B2033(Up to approximately 2 years)