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

NCT06427941 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: BGB-B2033-1012025-524136-19-00jRCT2051260010
• Study Type: interventional
• Target: 140
• Locations: 5 countries
• Sites: 20

Brief 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).

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

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Disease Control Rate (DCR)

  Up to approximately 2 years

• Progression Free Survival (PFS)

  Up to approximately 2 years

• Serum concentration of of BGB-B2033

  Up to approximately 2 years

Study Arms (2)

Part A (Monotherapy Dose Escalation and Safety Expansion)

EXPERIMENTAL

Ascending dose levels of BGB-B2033 monotherapy

Drug: BGB-B2033

Part B (Combination Dose Escalation and Safety Expansion)

EXPERIMENTAL

Cohorts of BGB-B2033 in combination with tislelizumab

Drug: BGB-B2033; Drug: Tislelizumab; Drug: Bevacizumab

Interventions

BGB-B2033 DRUG

Administered by intravenous infusion

Part A (Monotherapy Dose Escalation and Safety Expansion); Part B (Combination Dose Escalation and Safety Expansion)

Tislelizumab DRUG

Administered by intravenous infusion

Part B (Combination Dose Escalation and Safety Expansion)

Bevacizumab DRUG

Administered by intravenous infusion

Part B (Combination Dose Escalation and Safety Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have one of the following unresectable, locally advanced, or metastatic tumor types:
• 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.
• 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.
• 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.
• 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).
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Adequate organ function as defined in the protocol.
• Provision of tumor tissue samples is required for specified parts of the study.

You may not qualify if:

• Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137).
• Active leptomeningeal disease or uncontrolled/untreated brain metastases.
• Active autoimmune disease or a history of autoimmune disease with potential for relapse.
• 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.
• 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).
• Certain comorbidities involving the lungs, heart, bleeding conditions, or active infections, as defined in the protocol.

Sponsors & Collaborators

• BeOne Medicines: lead

Study Sites (20)

Memorial Sloan Kettering Cancer Center Mskcc

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

RECRUITING

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Pittsburgh, Pennsylvania, 15232-1309, United States

RECRUITING

Scri Oncology Partners

Nashville, Tennessee, 37203-1503, United States

RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

RECRUITING

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, 350025, China

RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

RECRUITING

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

The Second Affiliated Hospital of Nanchang Universityhongjiaozhou Branch

Nanchang, Jiangxi, 330038, China

RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

Auckland City Hospital

Auckland, 1023, New Zealand

RECRUITING

Hospital Oncologico

Rio Piedras, 00935, Puerto Rico

RECRUITING

Cha Bundang Medical Center, Cha University

BundangGu SeongnamSi, Gyeonggi-do, 13496, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

Samsung Medical Center

GangnamGu, Seoul Teugbyeolsi, 06351, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

SeodaemunGu, Seoul Teugbyeolsi, 03722, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 03080, South Korea

RECRUITING

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi, 05505, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Simpson-Golabi-Behmel syndrome

Interventions

tislelizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Central Study Contacts

Study Director

CONTACT

1.877.828.5568; clinicaltrials@beonemed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: July 23, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

NZ (1); KR (6); US (3); CN (9); PR (1)