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

Phase 3Not Yet RecruitingNCT07836530

BeOne Medicines492 enrolled

Overview

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?

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It can develop when abnormal cells in the liver grow uncontrollably and may spread to other parts of the body. For people whose cancer has returned or continued to grow after treatment, additional treatment options are needed. BGB-B2033 is a new investigational drug designed to bind to a protein called glypican-3 (GPC3), a protein found on certain cancer cells and cells of the immune system, helping the immune system to recognize and attack the cancer cells. Lenvatinib and sorafenib are approved medicines that work by blocking signals that help cancer cells grow and form new blood vessels. The purpose of this study is to test whether BGB-B2033 is safe and can help treat HCC in adults whose cancer has been treated with up to 2 previous treatments that included programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) medicines. The main goal of the study is to see how well BGB-B2033 controls cancer compared to the treatments selected by the study doctor (either lenvatinib or sorafenib). This study has 2 treatment groups. Participants will be randomly assigned, like flipping a coin, to receive either: * BGB-B2033, given by intravenous infusion. * Sorafenib, taken by mouth or lenvatinib, taken by mouth per their doctor's choice The study will enroll approximately 492 adults with HCC at multiple centers worldwide. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and tumor and imaging tests. The overall study will last about 3.5 years, not including the screening period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Participants must have histologically confirmed Hepatocellular Carcinoma (HCC) that is not amenable to curative surgical or locoregional therapies. 2. 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. 3. Glypican-3 (GPC3) expression level must be known for stratification. 4. Participants must have at least 1 measurable lesion as assessed by RECIST v1.1 5. Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1. Key Exclusion Criteria: 1. Prior therapy targeting GPC3 or 4-1BB 2. Participants not feasible to be treated with lenvatinib or sorafenib 1. prior exposure to both medications 2. 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, 3. any history of gastrointestinal perforation or larger than grade 3 fistula within 6 months prior to the first dose, 4. or any history of heart failure meeting NYHA classification III or IV ≤ 6 months before the first dose of study drug. 3. Active leptomeningeal disease or uncontrolled and untreated brain metastasis 4. History of previous or present encephalopathy 5. Presence of clinically significant ascites ((≥ Grade 2). 6. History of liver transplantation NOTE: Other eligbility criteria may apply.

Outcomes

Primary Outcomes

Overall Survival (OS)

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

Time frame: Up to approximately 3.5 years

Secondary Outcomes

Overall Response Rate (ORR)

Defined as the percentage of participants who achieved complete response (CR) or partial response (PR) by investigator assessment and Blinded Independent Central Review (BICR) with confirmation per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Time frame: Up to approximately 3.5 years

Duration of Response (DOR)

DOR is defined as the time from the date that a confirmed response (CR or PR) was first observed to the date of first documented disease progression or death, whichever occurred first. Assessed by BIRC and investigator with confirmation per RECIST v1.1.

Time frame: Up to approximately 3.5 years

Progression Free Survival Rate (PFS)

PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first as determined by investigator assessment and BIRC with confirmation per RECIST v1.1

Time frame: 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)

Safety will be assessed by monitoring and recording of all adverse events (AEs) graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v6.0.

Time frame: 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

The EORTC QLQ-HCC18 measures health related quality of life outcomes in participants with liver cancer. The 18-item questionnaire is conceptualized as consisting of 6 symptom domains, 2 single items and an Index score: fatigue (3 items), body image (2 items), jaundice (2 items), nutrition (5 items), pain (2 items), fever (2 items), abdominal swelling (1 item), and sex life (1 item). The Index score is a composite of all 18 items. The items are scored using a verbal-descriptive scale rated from 1 to 4 (1 = "not at all"; 4 = "very much"). Higher scores indicate worse symptoms.

Time frame: 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.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Function 17 (EORTC QLQ-F17) Global Health Status (GHS), and Physical/Role Functioning scores

The EORTC QLQ-F17 is a generic core questionnaire that assesses self-reported functioning and GHS in participants with cancer. The EORTC QLQ-F17 includes predefined key participant reported outcomes (PRO) endpoints to measure GHS and physical functioning and role functioning. The functional items are scored on a 4-point verbal-descriptive scale (1 = "not at all"; 4 = "very much"), while the 2 GHS items use a 7-point scale (1 = "very poor"; 7 = "excellent"). Higher scores in GHS and functioning scales indicate better health related quality outcomes.

Time frame: 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.

Time to Deterioration of Fatigue Measured by EORTC QLQ-HCC18

Time to deterioration in fatigue, as measured by the fatigue domain of the EORTC QLQ-HCC18 questionnaire. The fatigue domain consists of 3 items scored from 1 ("not at all") to 4 ("very much"). Higher scores indicate worse fatigue. Time to deterioration is defined as the time from randomization to the first clinically meaningful worsening in the fatigue score from baseline, based on the prespecified scoring criteria.

Time frame: From randomization until the first clinically meaningful deterioration, end of treatment, withdrawal of consent, death, or end of study, as applicable (Up to approximately 3.5 years)

Time to Deterioration of Global Health Status and Physical/Role Functioning Measured by EORTC QLQ-F17.

Time to deterioration in global health status, physical functioning, and role functioning, as measured by the EORTC QLQ-F17 questionnaire. The questionnaire assesses participants' self-reported overall health, physical functioning, and ability to perform daily activities and roles. Higher scores indicate better health-related quality of life. Time to deterioration is defined as the time from randomization to the first clinically meaningful worsening from baseline in global health status, physical functioning, or role functioning, based on prespecified scoring criteria.

Time frame: From randomization until the first clinically meaningful deterioration, end of treatment, withdrawal of consent, death, or end of study, as applicable ((Up to approximately 3.5 years).

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts