Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06427941

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

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).

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Metastatic Hepatocellular Carcinoma Adenocarcinoma Alpha-fetoprotein (AFP)-Producing Gastric Cancer Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Extragonadal Yolk Sac Tumors Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer Liver Diseases Liver Neoplasms Local Advanced Hepatocellular Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Simpson-Golabi-Behmel syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Centro Gaucho Integrado de Oncologia Hospital Mae de Deus, Porto Alegre, Brazil

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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 1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
  • Adequate organ function as defined in the protocol.
  • 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.

Treatment and study plan

BGB-B2033

Drug

Administered by intravenous infusion

Tislelizumab

Drug

Administered by intravenous infusion

Bevacizumab

Drug

Administered by intravenous infusion

Primary outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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).

Secondary outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Director

CONTACT

[email protected]

1.877.828.5568

Sponsors and collaborators

Lead sponsor

BeOne Medicines

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
May 24, 2024
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.