Recruiting
Phase 1
Phase 2

BGB-B2033 & Tislelizumab

Sponsor:

BeOne Medicines

Code:

NCT06427941

Conditions

Metastatic Hepatocellular Carcinoma

Local Advanced Hepatocellular Carcinoma

Alpha-fetoprotein (AFP)-Producing Gastric Cancer

Extragonadal Yolk Sac Tumors

Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BGB-B2033

Tislelizumab

Bevacizumab

Study Details

Brief summary:

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.

Conditions

Metastatic Hepatocellular Carcinoma

Local Advanced Hepatocellular Carcinoma

Alpha-fetoprotein (AFP)-Producing Gastric Cancer

Extragonadal Yolk Sac Tumors

Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer

Study ID

NCT06427941

Start date

Jul 23, 2024

Status verified date

Sep, 2026

Completion date

Oct 31, 2028

Anticipated

Primary completion date

Mar 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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.

Study Design

Enrollment

630 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A (Monotherapy Dose Escalation and Safety Expansion)

Participants will receive ascending dose levels of BGB-B2033 monotherapy

experimental: Part B (Doublet Run-in)

Participants will receive BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation.

experimental: Part B (Triplet Dose Escalation)

Participants will receive 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.

experimental: Part B (Triplet and Doublet Safety Expansion)

Safety expansion arm for each combination therapy cohort (triplet and doublet)

experimental: Part C (Asia Monotherapy Dose Expansion in HCC)

Participants in Asian countries with HCC will receive BGB-B2033 as monotherapy.

experimental: Part D (US Monotherapy Dose Expansion in HCC)

Participants in the United States (US) with HCC will receive BGB-B2033 as monotherapy.

experimental: Part E (Monotherapy Dose Expansion in HCC)

Participants with HCC will receive BGB-B2033 as monotherapy.

Interventions

BGB-B2033

Administered by intravenous infusion

Tislelizumab

Administered by intravenous infusion

Bevacizumab

Administered by intravenous infusion

Primary outcome measure

  • Part A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 2 years ]
  • Part A and B: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033 [ Time Frame: Up to approximately 2 years ]
  • Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033 [ Time Frame: Up to approximately 2 years ]
  • Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) [ Time Frame: Up to approximately 2 years ]

Central Contacts and Locations

Central contacts

Locations

University of Alabama At Birmingham Hospital

Recruiting

Birmingham, Alabama, United States, 35294-0004

City of Hope Phoenix Cancer Center

Recruiting

Goodyear, Arizona, United States, 85338

City of Hope National Medical Center

Recruiting

Duarte, California, United States, 91010-3012

City of Hope Chicago Cancer Center

Recruiting

Zion, Illinois, United States, 60099

Memorial Sloan Kettering Cancer Center Mskcc

Recruiting

New York, New York, United States, 10065-6800

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232-1309

Scri Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203-1503

The University of Texas Md Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4009

More Information

Sponsor

BeOne Medicines

Last update posted

Sep 16, 2026

Last verified

Sep, 2026

Keywords

  • GPC-3
  • GPC3-positive squamous non-small cell lung cancer
  • BGB-B2033
  • tislelizumab
  • hepatocellular carcinoma
  • alpha-fetoprotein (AFP)-producing gastric cancer
  • extragonadal yolk sac tumors
  • Bevacizumab

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-26. This information was provided to ClinicalTrials.gov by BeOne Medicines on 2026-09-16. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.