A Phase 1/2 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors
Purpose
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.
Conditions
- Metastatic Hepatocellular Carcinoma
- Local Advanced Hepatocellular Carcinoma
- Alpha-fetoprotein (AFP)-Producing Gastric Cancer
- Extragonadal Yolk Sac Tumors
- Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants must have one of the following unresectable, locally advanced, or metastatic tumor types: 1. 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. 2. 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. 3. 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. 4. 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). 2. 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 1.1. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. 4. Adequate organ function as defined in the protocol. 5. Provision of tumor tissue samples is required for specified parts of the study.
Exclusion Criteria
- Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137). 2. Active leptomeningeal disease or uncontrolled/untreated brain metastases. 3. Active autoimmune disease or a history of autoimmune disease with potential for relapse. 4. 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. 5. 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). 6. 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.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A (Monotherapy Dose Escalation and Safety Expansion) |
Participants will receive ascending dose levels of BGB-B2033 monotherapy |
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|
Experimental 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. |
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|
Experimental 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. |
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Experimental Part B (Triplet and Doublet Safety Expansion) |
Safety expansion arm for each combination therapy cohort (triplet and doublet) |
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|
Experimental Part C (Asia Monotherapy Dose Expansion in HCC) |
Participants in Asian countries with HCC will receive BGB-B2033 as monotherapy. |
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Experimental Part D (US Monotherapy Dose Expansion in HCC) |
Participants in the United States (US) with HCC will receive BGB-B2033 as monotherapy. |
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Experimental Part E (Monotherapy Dose Expansion in HCC) |
Participants with HCC will receive BGB-B2033 as monotherapy. |
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Recruiting Locations
Birmingham, Alabama 35294-0004
More Details
- Status
- Recruiting
- Sponsor
- BeOne Medicines