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Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A (Monotherapy Dose Escalation and Safety Expansion) 		Ascending dose levels of BGB-B2033 monotherapy
  • Drug: BGB-B2033
    Administered by intravenous infusion
Experimental
Part B (Doublet Run-in) 		A cohort designed to evaluate the safety and tolerability of BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation.
  • Drug: BGB-B2033
    Administered by intravenous infusion
  • Drug: Tislelizumab
    Administered by intravenous infusion
Experimental
Part B (Triplet Dose Escalation) 		Cohorts evaluating BGB-B2033 in combination with tislelizumab and bevacizumab to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDFE) of the combination.
  • Drug: BGB-B2033
    Administered by intravenous infusion
  • Drug: Tislelizumab
    Administered by intravenous infusion
  • Drug: Bevacizumab
    Administered by intravenous infusion
Experimental
Part B (Triplet and Doublet Safety Expansion) 		Safety expansion arm for each combination therapy cohort (triplet and doublet)
  • Drug: BGB-B2033
    Administered by intravenous infusion
  • Drug: Tislelizumab
    Administered by intravenous infusion
  • Drug: Bevacizumab
    Administered by intravenous infusion
Experimental
Part C (Asia Monotherapy Dose Expansion in HCC) 		Participants in Asian countries with HCC
  • Drug: BGB-B2033
    Administered by intravenous infusion
Experimental
Part D (US Monotherapy Dose Expansion in HCC) 		Participants in the United States (US) with HCC
  • Drug: BGB-B2033
    Administered by intravenous infusion

Recruiting Locations

City of Hope Phoenix Cancer Center
Goodyear, Arizona 85338

City of Hope National Medical Center
Duarte, California 91010-3012

City of Hope Chicago Cancer Center
Zion, Illinois 60099

Memorial Sloan Kettering Cancer Center Mskcc
New York, New York 10065-6800

Upmc Hillman Cancer Center(Univ of Pittsburgh)
Pittsburgh, Pennsylvania 15232-1309

Scri Oncology Partners
Nashville, Tennessee 37203-1503

The University of Texas Md Anderson Cancer Center
Houston, Texas 77030-4009

Hospital Oncologico
Rio Piedras, Puerto Rico 00935

More Details

Status
Recruiting
Sponsor
BeOne Medicines

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beonemed.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.