Alpha-fetoprotein (AFP)-Producing Gastric Cancer, Extragonadal Yolk Sac Tumors, Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer, Local Advanced Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma
Conditions
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
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.
Interventions
DRUGBGB-B2033
Administered by intravenous infusion
DRUGTislelizumab
Administered by intravenous infusion
DRUGBevacizumab
Administered by intravenous infusion
Sponsors
BeOne Medicines
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B: 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 |
| Part A and B: 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. |
| Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033 | 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 |
| Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B: Overall Response Rate (ORR) as assessed by the investigator | 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). |
| Part A and B: Duration of Response (DOR) as assessed by the investigator | 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. |
| Part A and B: Disease Control Rate (DCR) as assessed by the investigator | 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. |
| Part A and B: Progression Free Survival (PFS) as assessed by the investigator | 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 due to any cause, whichever occurs first. |
| 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 | — |
| Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Investigator | 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). |
| Parts C, D, and E: Duration of Response (DOR) as assessed by the investigator and IRC | 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. |
| Parts C, D, and E: Progression Free Survival (PFS) as assessed by the investigator and IRC | 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 due to any cause, whichever occurs first. |
| All Parts: Overall Survival (OS) | Up to approximately 2 years | OS is defined as the time from first dose to the death due to any cause. |
| Parts C, D, and E: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 2 years | 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. |
Countries
Brazil, China, France, Italy, Japan, New Zealand, Puerto Rico, South Korea, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed