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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Hepatocellular Carcinoma; Alpha-fetoprotein (AFP)-Producing Gastric Cancer; Extragonadal Yolk Sac Tumors; Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer; Local Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: BGB-B2033; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 392
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1.877.828.5568; Email: clinicaltrials@beonemed.com

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90110-270
    • Recruiting
    • Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
  • Salvador, Brazil, 41810-011
    • Recruiting
    • Hospital da Bahia
  • São José do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Recruiting
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350028
      • Recruiting
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
  • Guangxi
    • Nanning, Guangxi, China, 530201
      • Recruiting
      • Guangxi Medical University Cancer Hospital Wuxiang Branch
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin medical university cancer hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330038
      • Recruiting
      • The Second Affiliated Hospital of Nanchang Universityhongjiaozhou Branch
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Sichuan Cancer Hospital and Institute
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Lishui, Zhejiang, China, 323000
      • Recruiting
      • Lishui Central Hospital
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
• France
  • Clichy, France, 92110
    • Recruiting
    • Hopital Beaujon
  • Nantes, France, 44000
    • Recruiting
    • Centre Hospitalier Universitaire Nantes Hotel Dieu
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Irccs Istituto Nazionale Tumori Fondazione Pascale
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Rozzano, Italy, 20089
    • Recruiting
    • Irccs Humanitas Research Hospital
• Japan
  • Osaka
    • Sakai, Osaka, Japan, 590-0197
      • Recruiting
      • Kindai University Hospital
  • Tokyo
    • Bunkyoku, Tokyo, Japan, 113-8677
      • Recruiting
      • Tokyo Metropolitan Komagome Hospital
    • Kotoku, Tokyo, Japan, 135-8550
      • Recruiting
      • Cancer Institute Hospital of Jfcr
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Hospital Oncologico
• South Korea
  • Chungcheongbukdo
    • Cheongju-si, Chungcheongbukdo, South Korea, 28644
      • Recruiting
      • Chungbuk National University Hospital
  • Gyeonggi-do
    • BundangGu SeongnamSi, Gyeonggi-do, South Korea, 13496
      • Recruiting
      • CHA Bundang Medical Center, CHA University
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • GangnamGu, Seoul Teugbyeolsi, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
    • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
      • Recruiting
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
    • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
      • Recruiting
      • Asan Medical Center
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Recruiting
      • City of Hope Phoenix Cancer Center
  • California
    • Duarte, California, United States, 91010-3012
      • Recruiting
      • City of Hope National Medical Center
  • Illinois
    • Zion, Illinois, United States, 60099
      • Recruiting
      • City of Hope Chicago Cancer Center
  • New York
    • New York, New York, United States, 10065-6800
      • Recruiting
      • Memorial Sloan Kettering Cancer Center Mskcc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232-1309
      • Recruiting
      • Upmc Hillman Cancer Center(Univ of Pittsburgh)
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1503
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Tislelizumab; Administered by intravenous infusion; Drug: BGB-B2033; 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: Tislelizumab; Administered by intravenous infusion; Drug: BGB-B2033; 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: Tislelizumab; Administered by intravenous infusion; Drug: BGB-B2033; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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	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).	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and B: Overall Response Rate (ORR) as assessed by the investigator	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).	Up to approximately 2 years
Part A and B: Duration of Response (DOR) as assessed by the investigator	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.	Up to approximately 2 years
Part A and B: Disease Control Rate (DCR) as assessed by the investigator	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.	Up to approximately 2 years
Part A and B: Progression Free Survival (PFS) as assessed by the investigator	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.	Up to approximately 2 years
Part A and B: Serum concentration of of BGB-B2033		Up to approximately 2 years
Part A and B: Number of participants with anti-drug antibodies (ADAs) to BGB-B2033		Up to approximately 2 years
Part C and D: Overall Response Rate (ORR) as assessed by the investigator	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).	Up to approximately 2 years
Part C and D: Duration of Response (DOR) as assessed by the investigator and IRC	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.	Up to approximately 2 years
Part C and D: Progression Free Survival (PFS) as assessed by the investigator and IRC	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.	Up to approximately 2 years
Part C and D: Overall Survival (OS)	OS is defined as the time from first dose to the death due to any cause.	Up to approximately 2 years
Part C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2024
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Bevacizumab; hepatocellular carcinoma; tislelizumab; GPC-3; GPC3-positive squamous non-small cell lung cancer; BGB-B2033; alpha-fetoprotein (AFP)-producing gastric cancer; extragonadal yolk sac tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Simpson-Golabi-Behmel syndrome; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; tislelizumab
• Other Study ID Numbers: BGB-B2033-101 (Registry Identifier: Chinadrugtrials); 2025-524136-19-00 (Ctis); jRCT2051260010 (Other Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No