A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

• Conditions: Metastatic Hepatocellular Carcinoma; Advanced Hepatocellular Carcinoma; Alpha-fetoprotein (AFP)-Producing Gastric Cancer; Extragonadal Yolk Sac Tumors; Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer; Metastatic Solid Tumor
• Interventions: Drug: BGB-B2033; Drug: Tislelizumab

• Registration Number: NCT06427941
• Lead Sponsor: BeiGene

Brief Summary

This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of the BGB-B2033 in participants 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 identify the recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab for subsequent studies. BGB-B2033 will be administered by intravenous infusion. The Phase 1 study will be conducted in 2 parts: Part A (Monotherapy Dose Escalation and Safety Expansion) and Part B (Combination Dose Escalation and Safety Expansion).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-20
• Study First Submitted QC: 2024-05-20
• Study First Posted: 2024-05-24
• Study Start: 2024-07-23
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-16
• Primary Completion: 2026-10-30
• Study Completion: 2026-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Participants with any of the following unresectable locally advanced or metastatic tumor types:

   1. HCC
   2. AFP-producing GC (serum AFP > 20 ng/mL or tumor tissue AFP positive by a validated IHC assay according to local testing criteria)
   3. germ cell tumor including extragonadal yolk sac tumors (located in mediastinum, vagina, brain, and retroperitoneum, etc) and non-dysgerminomas
   4. GPC3-positive squamous NSCLC

2. ≥ 1 evaluable lesion for dose escalation and ≥ 1 measurable lesion for safety expansion, per RECIST v1.1

3. ECOG Performance Status score ≤ 1

4. Adequate organ functions

5. Tumor tissues will be required for certain parts of the study

Exclusion Criteria

1. Prior therapy targeting glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (also known as CD137)
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
3. Active autoimmune diseases or history of autoimmune diseases that may relapse
4. Any malignancy ≤ 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
5. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
6. Certain comorbidities in the lung, heart, bleeding condition and infections.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A (Monotherapy Dose Escalation and Safety Expansion)	BGB-B2033	Ascending dose levels of BGB-B2033 monotherapy
Part B (Combination Dose Escalation and Safety Expansion)	BGB-B2033	Cohorts of BGB-B2033 in combination with tislelizumab
Part B (Combination Dose Escalation and Safety Expansion)	Tislelizumab	Cohorts of BGB-B2033 in combination with tislelizumab

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to approximately 2 years	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;
Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033	Up to approximately 2 years	The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.
Recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab	Up to approximately 2 years	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

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to approximately 2 years	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).
Duration of Response (DOR)	Up to approximately 2 years	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.
Disease Control Rate (DCR)	Up to approximately 2 years	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.
Progression Free Survival (PFS)	Up to approximately 2 years	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, whichever occurs first.
Serum concentration of BGB-B2033	Up to approximately 2 years
Number of participants with anti-drug antibodies (ADAs) to BGB-B2033	Up to approximately 2 years

Trial Locations

Locations (15)

Scri Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Upmc Hillman Cancer Center; 🇺🇸 Puyallup, Washington, United States

Anhui Provincial Hospital; 🇨🇳 Hefei, Anhui, China

Memorial Sloan Kettering Cancer Center Mskcc; 🇺🇸 New York, New York, United States

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, Heilongjiang, China

Mengchao Hepatobiliary Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

Nanfang Hospital of Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Cha Bundang Medical Center, Cha University; 🇰🇷 BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

The Second Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Samsung Medical Center; 🇰🇷 GangnamGu, Seoul Teugbyeolsi, Korea, Republic of

Severance Hospital Yonsei University Health System; 🇰🇷 SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of

Auckland City Hospital; 🇳🇿 Auckland, New Zealand