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RecruitingInterventionalPhase 1

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

NCT ID: NCT06427941Sponsor: BeOne MedicinesLast updated: 2026-06-03

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).

Arms & interventions

  • DrugBGB-B2033

    Administered by intravenous infusion

  • DrugTislelizumab

    Administered by intravenous infusion

  • DrugBevacizumab

    Administered by intravenous infusion

Outcome measures

Primary

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

    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

    Time frame: Up to approximately 2 years

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

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

    Time frame: Up to approximately 2 years

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

    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

    Time frame: Up to approximately 2 years

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

    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).

    Time frame: Up to approximately 2 years

Secondary

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

  • Part A and B: Serum concentration of of BGB-B2033

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

  • Part C and D: Overall Survival (OS)

    Time frame: Up to approximately 2 years

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

    Time frame: Up to approximately 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (7)

City of Hope Phoenix Cancer Center

Goodyear, Arizona, 85338

Recruiting

City of Hope National Medical Center

Duarte, California, 91010-3012

Recruiting

City of Hope Chicago Cancer Center

Zion, Illinois, 60099

Recruiting

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, 10065-6800

Recruiting

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Pittsburgh, Pennsylvania, 15232-1309

Recruiting

Scri Oncology Partners

Nashville, Tennessee, 37203-1503

Recruiting

The University of Texas Md Anderson Cancer Center

Houston, Texas, 77030-4009

Recruiting