Dysautonomia International

A Phase 1/2 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors

Purpose

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.

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

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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.

Exclusion Criteria

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 Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: N/A
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part A (Monotherapy Dose Escalation and Safety Expansion)	Participants will receive ascending dose levels of BGB-B2033 monotherapy	Drug: BGB-B2033 Administered by intravenous infusion
Experimental Part B (Doublet Run-in)	Participants will receive BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation.	Drug: BGB-B2033 Administered by intravenous infusion Drug: Tislelizumab Administered by intravenous infusion
Experimental Part B (Triplet Dose Escalation)	Participants will receive 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: BGB-B2033 Administered by intravenous infusion Drug: Tislelizumab 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: BGB-B2033 Administered by intravenous infusion Drug: Tislelizumab 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 will receive BGB-B2033 as monotherapy.	Drug: BGB-B2033 Administered by intravenous infusion
Experimental Part D (US Monotherapy Dose Expansion in HCC)	Participants in the United States (US) with HCC will receive BGB-B2033 as monotherapy.	Drug: BGB-B2033 Administered by intravenous infusion
Experimental Part E (Monotherapy Dose Expansion in HCC)	Participants with HCC will receive BGB-B2033 as monotherapy.	Drug: BGB-B2033 Administered by intravenous infusion

Recruiting Locations

City of Hope Phoenix Cancer Center
Goodyear, Arizona 85338

City of Hope National Medical Center
Duarte, California 91010-3012

City of Hope Chicago Cancer Center
Zion, Illinois 60099

Memorial Sloan Kettering Cancer Center Mskcc
New York, New York 10065-6800

Upmc Hillman Cancer Center(Univ of Pittsburgh)
Pittsburgh, Pennsylvania 15232-1309

Scri Oncology Partners
Nashville, Tennessee 37203-1503

The University of Texas Md Anderson Cancer Center
Houston, Texas 77030-4009

Hospital Oncologico
Rio Piedras, Puerto Rico 00935

More Details

Status: Recruiting
Sponsor: BeOne Medicines

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beonemed.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.