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

Sponsor score: 0

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

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

  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 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.

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.

Locations

FACILITYZIPCITYSTATE
University of Alabama At Birmingham Hospital35294-0004BirminghamAlabama
City of Hope Phoenix Cancer Center85338GoodyearArizona
City of Hope National Medical Center91010-3012DuarteCalifornia
City of Hope Chicago Cancer Center60099ZionIllinois
Memorial Sloan Kettering Cancer Center Mskcc10065-6800New YorkNew York
Upmc Hillman Cancer Center(Univ of Pittsburgh)15232-1309PittsburghPennsylvania
Scri Oncology Partners37203-1503NashvilleTennessee
The University of Texas Md Anderson Cancer Center77030-4009HoustonTexas

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