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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: BGB-58067; Drug: BG-89894; Drug: Standard of Care Therapy

• Registration Number: NCT06589596
• Lead Sponsor: BeiGene

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-09-06
• Study First Submitted QC: 2024-09-06
• Study First Posted: 2024-09-19
• Study Start: 2024-10-11
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-22
• Last Update Posted: 2025-10-24
• Primary Completion: 2027-06
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 237

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
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1a: BGB-58067 Monotherapy Dose Escalation and Safety Expansion	BGB-58067	Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated.
Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation	BGB-58067	Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.
Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation	BG-89894	Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.
Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation	BGB-58067	Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.
Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation	Standard of Care Therapy	Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.
Phase 1b: Dose Expansion and Optimization	BGB-58067	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.
Phase 1b: Dose Expansion and Optimization	BG-89894	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.
Phase 1b: Dose Expansion and Optimization	Standard of Care Therapy	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.

Primary Outcome Measures

Name	Time	Method
Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events	From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months)	Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria	From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 1 month)
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy	Approximately 1 month	MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy	Approximately 13 months	RDFE of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be determined based upon the MTD or MAD.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy	Approximately 2 years	RP2D established from Phase 1a for BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy for administration in selected tumor types.
Phase 1b: Objective Response Rate (ORR)	Approximately 2 years	ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR), as assessed by the investigator.

Secondary Outcome Measures

Name	Time	Method
Phase 1a: Objective Response Rate (ORR)	Approximately 2 years	ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator.
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067	Approximately 2 months
Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067	Approximately 9 months
Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067	Approximately 2 months
Phase 1a and 1b: Apparent oral clearance (CL/F) for BGB-58067	Approximately 2 months
Phase 1a and 1b: Half-life (t1/2) of BGB-58067	Approximately 2 months
Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-58067	Approximately 2 months
Phase 1a and 1b: Apparent volume of distribution (Vz/F) for BGB-58067	Approximately 2 months
Phase 1a and 1b: Accumulation ratio (AR) for BGB-58067	Approximately 2 months
Phase 1a and 1b: Plasma concentrations of BGB-58067	Approximately 9 months
Phase 1a and 1b: Duration of Response (DOR)	Approximately 2 years	DOR is defined as the time from the first determination of an objective response until first documentation of progression or death, whichever occurs first, as assessed by the investigator.
Phase 1a and 1b: Disease Control Rate (DCR)	Approximately 2 years	DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease, as assessed by the investigator.
Phase 1b: Number of Participants with AEs and SAEs	From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months)	Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Phase 1b: Progression-Free Survival (PFS)	Approximately 2 years	PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease assessed by investigator or death, whichever occurs first, as assessed by the investigator.

Trial Locations

Locations (36)

Usc Norris Comprehensive Cancer Center (Nccc); 🇺🇸 Los Angeles, California, United States

Adventhealth; 🇺🇸 Celebration, Florida, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 St Louis, Missouri, United States

Nyu Langone Health; 🇺🇸 New York, New York, United States

Sidney Kimmel Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

The University of Texas Md Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Next Dallas; 🇺🇸 Irving, Texas, United States

Next Virginia; 🇺🇸 Fairfax, Virginia, United States

Blacktown Cancer and Haematology Centre; 🇦🇺 Blacktown, New South Wales, Australia

Scroll for more (26 remaining)