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
Sponsor: BeOne Medicines
ClinicalTrials ID:NCT06427941
This Phase 1/2 trial assesses BGB-B2033's safety, PK/PD, and antitumor activity in advanced/metastatic cancers, including HCC and GPC3-positive NSCLC. Eligible participants must have specific tumor types, measurable lesions, ECOG ≤ 1, and adequate organ function. Interventions include BGB-B2033, alone or with tislelizumab and/or bevacizumab, all via IV infusion.
Patient Parameters
| Parameter | Options |
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Program Overview
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.
Eligibility Criteria
Inclusion Criteria
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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).
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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.
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Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
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Adequate organ function as defined in the protocol.
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Provision of tumor tissue samples is required for specified parts of the study.
Key
Exclusion Criteria
- 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.
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| University of Alabama At Birmingham Hospital | 35294-0004 | Birmingham | Alabama |
| City of Hope Phoenix Cancer Center | 85338 | Goodyear | Arizona |
| City of Hope National Medical Center | 91010-3012 | Duarte | California |
| City of Hope Chicago Cancer Center | 60099 | Zion | Illinois |
| Memorial Sloan Kettering Cancer Center Mskcc | 10065-6800 | New York | New York |
| Upmc Hillman Cancer Center(Univ of Pittsburgh) | 15232-1309 | Pittsburgh | Pennsylvania |
| Scri Oncology Partners | 37203-1503 | Nashville | Tennessee |
| The University of Texas Md Anderson Cancer Center | 77030-4009 | Houston | Texas |
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