A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors

NCT06427941
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
392
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Lead sponsor
BeOne Medicines
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Start date
2024-07-23
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Number of sites
48
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Summary
This is a first-in-human (FIH) clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of BGB-B2033 administered as monotherapy and in combination with tislelizumab, with or without bevacizumab. The study will enroll participants with locally 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).
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Short title
A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors
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Official title
A Phase 1 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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-05-30
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First posted
2024-05-24
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Registry last updated
2026-07-29
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Primary completion date
2028-05-30
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Start date
2024-07-23
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Participants
392
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Participant count basis
Estimated
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Planned participants
392
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Protocol amendments
6
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Number of sites
48
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
BeOne Medicines
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06427941
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ClinicalTrials.gov ID
NCT06427941
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Part A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: 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

  2. Part A and B: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033

    Timeframe: Up to approximately 2 years

    The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.

  3. Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033

    Timeframe: 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

  4. Part C and D: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC)

    Timeframe: 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).

  1. Part A and B: Overall Response Rate (ORR) as assessed by the investigator

    Timeframe: 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).

  2. Part A and B: Duration of Response (DOR) as assessed by the investigator

    Timeframe: Up to approximately 2 years

    DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first.

  3. Part A and B: Disease Control Rate (DCR) as assessed by the investigator

    Timeframe: Up to approximately 2 years

    DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments using RECIST v1.1.

  4. Part A and B: Progression Free Survival (PFS) as assessed by the investigator

    Timeframe: Up to approximately 2 years

    PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease using RECIST v1.1 or death due to any cause, whichever occurs first.

  5. Part A and B: Serum concentration of of BGB-B2033

    Timeframe: Up to approximately 2 years

  6. Part A and B: Number of participants with anti-drug antibodies (ADAs) to BGB-B2033

    Timeframe: Up to approximately 2 years

  7. Part C and D: Overall Response Rate (ORR) as assessed by the investigator

    Timeframe: 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).

  8. Part C and D: Duration of Response (DOR) as assessed by the investigator and IRC

    Timeframe: Up to approximately 2 years

    DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first.

  9. Part C and D: Progression Free Survival (PFS) as assessed by the investigator and IRC

    Timeframe: Up to approximately 2 years

    PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease using RECIST v1.1 or death due to any cause, whichever occurs first.

  10. Part C and D: Overall Survival (OS)

    Timeframe: Up to approximately 2 years

    OS is defined as the time from first dose to the death due to any cause.

  11. Part C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: Up to approximately 2 years

    Number of participants experiencing adverse events (AEs) and serious adverse events (SAEs), characterized by type, frequency, and severity. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0), and, where applicable, according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Events will also be described by timing of onset, seriousness, and assessed relationship to the study therapy. In addition, adverse events meeting protocol-defined adverse events of clinical interest (AECIs) will be specifically evaluated. Laboratory abnormalities will be summarized as part of the overall safety assessment.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  1. 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

  3. At least one measurable lesion for safety expansion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.

  5. Adequate organ function as defined in the protocol.

  6. Provision of tumor tissue samples is required for specified parts of the study.

Key Exclusion Criteria:

  1. 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.

Sources for eligibility
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  • City of Hope Phoenix Cancer CenterGoodyear, United StatesRecruiting
  • City of Hope National Medical CenterDuarte, United StatesRecruiting
  • City of Hope Chicago Cancer CenterZion, United StatesRecruiting
  • Memorial Sloan Kettering Cancer Center MskccNew York, United StatesRecruiting
  • Upmc Hillman Cancer Center(Univ of Pittsburgh)Pittsburgh, United StatesRecruiting
  • Scri Oncology PartnersNashville, United StatesRecruiting
  • The University of Texas Md Anderson Cancer CenterHouston, United StatesRecruiting
  • Centro Gaucho Integrado de Oncologia Hospital Mae de DeusPorto Alegre, BrazilRecruiting
  • Hospital Da BahiaSalvador, BrazilRecruiting
  • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio PretoSão José do Rio Preto, BrazilRecruiting
  • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de OliveiraSão Paulo, BrazilRecruiting
  • Anhui Provincial HospitalHefei, ChinaRecruiting
  • Chongqing University Cancer HospitalChongqing, ChinaRecruiting
  • Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, ChinaRecruiting
  • Zhujiang Hospital of Southern Medical UniversityGuangzhou, ChinaRecruiting
  • Nanfang Hospital of Southern Medical UniversityGuangzhou, ChinaRecruiting
  • Guangxi Medical University Cancer Hospital Wuxiang BranchNanning, ChinaRecruiting
  • The Fourth Hospital of Hebei Medical UniversityShijiazhuang, ChinaRecruiting
  • Harbin Medical University Cancer HospitalHarbin, ChinaRecruiting
  • Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaRecruiting
  • Tongji Hospital of Tongji Medical College Huazhong University of Science and TechnologyWuhan, ChinaRecruiting
  • Hunan Cancer HospitalChangsha, ChinaRecruiting
  • The Affiliated Hospital of Xuzhou Medical UniversityXuzhou, ChinaRecruiting
  • The Second Affiliated Hospital of Nanchang UniversityNanchang, ChinaRecruiting
  • The Second Affiliated Hospital of Nanchang Universityhongjiaozhou BranchNanchang, ChinaRecruiting

And 23 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-524136-19-00
  • jRCT2051260010
  • BGB-B2033-101
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (3)

Targets (2)