Study Comparing BGB-B2033 With Sorafenib or Lenvatinib in Relapsed Hepatocellular Carcinoma

NCT07836530 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BGB-B2033-3012026-526462-25-00
• Study Type: interventional
• Target: 492
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn how well BGB-B2033 works and how safe it is in people with hepatocellular carcinoma (HCC) who have previously received up to two treatments that included programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) medicines. Researchers will compare BGB-B2033 with either sorafenib or lenvatinib chosen by the study doctor to see which treatment works better and is safer. The main questions it aims to answer are:

• Does BGB-B2033 help control or slow the growth of liver cancer?
• What medical problems or side effects do participants have while taking BGB-B2033?
• Does BGB-B2033 help to prolong the survival for liver cancer participants over Lenvatinib/sorafenib?

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

Liver Cancer; Hepatocellular Carcinoma; Sorafenib; Lenvatinib; BGB-B2033

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the time from randomization to the date of death from any cause.

  Up to approximately 3.5 years

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  Up to approximately 3.5 years

• Duration of Response (DOR)

  Up to approximately 3.5 years

• Progression Free Survival Rate (PFS)

  Up to approximately 3.5 years

• Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (imAEs)

  From first dose until either 30 days after the last dose of study drug(s) or initiation of new anticancer therapy, whichever occurs first (Up to approximately 3.5 years)

• Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module [EORTC QLQ-HCC18]) Fatigue Scores

  From baseline (Cycle 1 Day 1, predose) through the Safety Follow-up Visit (30 days after last dose) with assessments every 2 cycles through EOT. Each cycle is 21 days.

Study Arms (2)

BGB-B2033

EXPERIMENTAL

Participants are randomized to receive BGB-B2033 until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first.

Drug: BGB-B2033

Investigator's choice: Lenvatinib OR sorafenib

ACTIVE COMPARATOR

Participants are randomized to receive either lenvatinib or sorafenib, selected by the investigator before treatment, until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first.

Drug: Lenvatinib; Drug: Sorafenib

Interventions

BGB-B2033 DRUG

Administered intravenously

BGB-B2033

Sorafenib DRUG

Administered by mouth as an oral tablet twice daily

Also known as: Nexavar

Investigator's choice: Lenvatinib OR sorafenib

Lenvatinib DRUG

Administered by mouth as an oral capsule once daily

Also known as: Lenvima

Investigator's choice: Lenvatinib OR sorafenib

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 histologically confirmed Hepatocellular Carcinoma (HCC) that is not amenable to curative surgical or locoregional therapies.
• Participants must have documented disease progression or intolerance after at least 1 but not exceeding 2 prior lines of systemic therapy containing Programmed Cell Death Protein 1 / Programmed Death-Ligand 1 (PD-1/PD-L1). Prior cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting therapy or v ascular endothelial growth factor (VEGF) is permitted but not required.
• Glypican-3 (GPC3) expression level must be known for stratification.
• Participants must have at least 1 measurable lesion as assessed by RECIST v1.1
• Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.

You may not qualify if:

• Prior therapy targeting GPC3 or 4-1BB
• Participants not feasible to be treated with lenvatinib or sorafenib
• prior exposure to both medications
• siginificant precautions of administering lenvatinib or sorafenib such as clinically significant active bleeding within 3 months prior to first dose, tumor thombus involving main portal vein trunk, inferior vena cava, or cardiac involvement,
• any history of gastrointestinal perforation or larger than grade 3 fistula within 6 months prior to the first dose,
• or any history of heart failure meeting NYHA classification III or IV ≤ 6 months before the first dose of study drug.
• Active leptomeningeal disease or uncontrolled and untreated brain metastasis
• History of previous or present encephalopathy
• Presence of clinically significant ascites ((≥ Grade 2).
• History of liver transplantation
• NOTE: Other eligbility criteria may apply.

Sponsors & Collaborators

• BeOne Medicines: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

lenvatinib; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2026
• First Posted: September 23, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): September 21, 2029
• Study Completion (Estimated): June 21, 2030
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

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