Testing BGB-B2033 alone or with Tislelizumab for advanced 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 study is testing a new treatment called BGB-B2033, alone or with another drug, to see if it can help people with advanced solid tumors feel better.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BeOne Medicines (industry)
• Drugs / interventions: prednisone, tislelizumab, bevacizumab
• Locations: 20 sites (New York, New York and 19 other locations)
• Trial ID: NCT06427941 on ClinicalTrials.gov

What this trial studies

This Phase 1 study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-B2033 in patients with advanced or metastatic solid tumors, including hepatocellular carcinoma and GPC3-positive squamous non-small cell lung cancer. The study consists of two parts: monotherapy dose escalation and safety expansion, and combination therapy with Tislelizumab. Participants will receive BGB-B2033 via intravenous infusion, and the study aims to determine the recommended Phase 2 dose for future research.

Who should consider this trial

Good fit: Ideal candidates include individuals with unresectable locally advanced or metastatic hepatocellular carcinoma, AFP-producing gastric cancer, extragonadal yolk sac tumors, or GPC3-positive squamous non-small cell lung cancer.

Not a fit: Patients with prior therapies targeting GPC3 or those with active autoimmune diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that are difficult to treat.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

Eligibility criteria

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.

Where this trial is running

New York, New York and 19 other locations

• Memorial Sloan Kettering Cancer Center Mskcc — New York, New York, United States (RECRUITING)
• Upmc Hillman Cancer Center(Univ of Pittsburgh) — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Scri Oncology Partners — Nashville, Tennessee, United States (RECRUITING)
• Anhui Provincial Hospital — Hefei, Anhui, China (RECRUITING)
• Mengchao Hepatobiliary Hospital of Fujian Medical University — Fuzhou, Fujian, China (RECRUITING)
• Nanfang Hospital of Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (RECRUITING)
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)
• Hunan Cancer Hospital — Changsha, Hunan, China (RECRUITING)
• The Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (RECRUITING)
• The Second Affiliated Hospital of Nanchang Universityhongjiaozhou Branch — Nanchang, Jiangxi, China (RECRUITING)
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)
• Auckland City Hospital — Auckland, New Zealand (RECRUITING)
• Hospital Oncologico — Rio Piedras, Puerto Rico (RECRUITING)
• Cha Bundang Medical Center, Cha University — BundangGu SeongnamSi, Gyeonggi-do, South Korea (RECRUITING)
• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea (RECRUITING)
• Samsung Medical Center — GangnamGu, Seoul Teugbyeolsi, South Korea (RECRUITING)
• Severance Hospital Yonsei University Health System — SeodaemunGu, Seoul Teugbyeolsi, South Korea (RECRUITING)
• Seoul National University Hospital — Seoul, Seoul Teugbyeolsi, South Korea (RECRUITING)
• Asan Medical Center — SongpaGu, Seoul Teugbyeolsi, South Korea (RECRUITING)

Study contacts

• Study coordinator: Study Director

Conditions: Metastatic Hepatocellular Carcinoma, Local Advanced Hepatocellular Carcinoma, Alpha-fetoprotein-Producing Gastric Cancer, Extragonadal Yolk Sac Tumors, Glypican-3-Positive Squamous Non-small Cell Lung Cancer, GPC-3, GPC3-positive squamous non-small cell lung cancer, BGB-B2033