An Investigational Study of BGB-58067 As a Single Agent and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors

BeOne Medicines

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: BG-89894; Drug: Standard of Care Therapy; Drug: BGB-58067

Study type: Interventional

Funder types: Industry

Identifiers

NCT06589596

BGB-58067-101

CTR20244451 (Registry Identifier)

2024-515307-19-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.

Full description

BGB-58067 is a new drug designed to target a specific protein called protein arginine methyltransferase 5 (PRMT5). This protein is involved in many cell activities and can promote cancer growth when it is overactive. High levels of PRMT5 are linked to poor outcomes in several types of cancer.

This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with MTAP deficiency.

Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Enrollment: 244 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must sign the ICF and be capable of giving written informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Scale (KPS) ≥ 70
• Life expectancy ≥ 3 months
• Evidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue
• Able to provide tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing
• Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose diseases have progressed or recurred after receiving standard systemic therapy or radiotherapy, or for whom standard systemic therapy is not available or tolerated, or would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard treatment in the opinion of the investigator; participants with advanced, metastatic, or unresectable solid tumors who have not received prior systemic treatment or have received one cycle of standard-of-care therapies will be enrolled in selected cohorts
• Adequate organ function

Exclusion criteria

• Prior treatment with any methylthioadenosine (MTA)-cooperative PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor
• Active leptomeningeal disease or symptomatic spinal cord compression
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
• Any malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively
• Significantly impaired pulmonary function
• Clinically significant infections
• Serologically active hepatitis B or C infection
• Known HIV infection. Participants with treated HIV infection may be included in Phase 1b if they meet certain criteria
• High cardiovascular risk factors
• QTcF > 470 ms based on the screening triplicate 12-lead ECG records and/or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome)
• Toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized
• Participants who are unable to swallow or with disease/procedure significantly affecting gastrointestinal function
• Female participants who are pregnant or are breastfeeding
• Concurrent participation in another therapeutic clinical study (participation in observational or noninterventional studies is allowed)

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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244 participants in 4 patient groups

Phase 1a: BGB-58067 Monotherapy Dose Escalation and Safety Expansion

Experimental group

Description:

Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated.

Treatment:

Drug: BGB-58067

Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation

Experimental group

Description:

Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.

Treatment:

Drug: BGB-58067

Drug: BG-89894

Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation

Experimental group

Description:

Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.

Treatment:

Drug: BGB-58067

Drug: Standard of Care Therapy

Phase 1b: Dose Expansion and Optimization

Experimental group

Description:

Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.

Treatment:

Drug: BGB-58067

Drug: Standard of Care Therapy

Drug: BG-89894