An Investigational Study of BG-89894 Tablets in Participants With Advanced Solid Tumors

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-89894 (SYH2039) Tablets in Patients With Advanced Solid Tumors

This study is being done to learn more about a new drug called BG-89894 (previously known as SYH2039). Researchers want to see if the drug is safe, how well people can tolerate it, how it moves through the body, and whether it shows any early signs of helping to treat cancer. The information gathered may help guide how future studies are designed. The entire study is expected to last about four years. People who join the study may receive treatment for around six months and will be followed for about 12 months after their treatment ends. The study plans to enroll participants over a three-year period.

Study Overview

• Status: Terminated
• Conditions: Advanced or Metastatic MTAP-deleted Solid Tumors
• Intervention / Treatment: Drug: BG-89894

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Blacktown Cancer and Haematology Centre
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Cancer Research South Australia
  • Victoria
    • Fitzroy, Victoria, Australia, VIC 3065
      • St Vincents Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Linear Clinical Research
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing Municipality, China, 102218
      • Beijing Tsinghua Changgung Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Provincial Peoples Hospital Huifu Branch
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Cancer Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110167
      • The First Hospital of China Medical University Hunnan Branch
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer At Johns Hopkins
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia University Irving Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Next Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must sign a written informed consent and willing to comply with all study-related procedures and requirements.
• Age ≥18 years (or the legal age of consent according to local regulations).
• Histologically or cytologically confirmed diagnosis of advanced, metastatic, or unresectable solid tumors that have progressed on or after standard therapy, or for which no appropriate standard therapy is available.
• Evidence of Methylthioadenosine phosphorylase (MTAP) homozygous deletion or loss of MTAP expression in tumor tissue.
• Participants must be able to provide an archived tumor tissue sample or unstained fresh biopsy if there is no archival tissue at baseline.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and evidence of adequate organ function and bone marrow reserve, as defined in the study protocol.

Key Exclusion Criteria:

• History of other malignancies or concurrent active malignancies within 3 years.
• Prior treatment with methionine adenosyltransferase 2 alpha (MAT2A) inhibitors (e.g., AG-270, IDE397) or methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitors (e.g., AMG193).
• Uncontrolled or active central nervous system (CNS) disease, including untreated or symptomatic brain metastases, spinal cord compression, or leptomeningeal carcinomatosis.
• Active bleeding, history of major bleeding events within the past 6 months, or tumors associated with a high risk of vascular invasion.
• Receipt of systemic anticancer therapy, radiation therapy, live vaccine, or major surgical procedures within protocol-specified washout periods.
• Active or uncontrolled infections, including tuberculosis (TB), (COVID-19, known human immunodeficiency virus (HIV) infection, or uncontrolled hepatitis B virus (HBV) infection.

Note: Additional eligibility criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Dose Escalation and Safety Expansion; Sequential cohorts of increasing dose levels of BG-89894 (SYH2039) will be evaluated as monotherapy.	Drug: BG-89894; Administered orally; Other Names: SYH2039
Experimental: Phase 1b: Dose Expansion and Optimization; Multiple indication-specific cohorts will be evaluated for safety, tolerability, and potential dose optimization of BG-89894 (SYH2039).	Drug: BG-89894; Administered orally; Other Names: SYH2039

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)	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.	Approximately 1 month
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants experiencing adverse events and serious adverse events as determined per Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.	From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 18 months)
Phase 1a: Recommended dose(s) for expansion (RDFE) of BG-89894	RDFE is defined as dose level(s) recommended for expansion that will be determined based on the MTD or MAD, taking into consideration the longterm tolerability, pharmacokinetics, pharmacodynamics, preliminary antitumor activity, and any other relevant data, as available.	Approximately 18 months
Phase 1b: Recommended Phase 2 Dose (RP2D)	R2PD is defined as the dose level recommended for phase 2 that will be determined based on safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary antitumor activity, and other relevant data.	Approximately 18 months
Phase 1b: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Approximately 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-89894		Twice in the first month
Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-89894		Twice in the first month
Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-89894		Twice in the first month
Phase 1a and 1b: Apparent volume of distribution (Vd/F) of BG-89894		Twice in the first month
Phase 1a and 1b: Apparent total clearance (CL/F) of BG-89894		Twice in the first month
Phase 1a and 1b: Area under the concentration-time curve (AUC) for BG-89894		Twice in the first month
Phase 1b: Minimum observed plasma concentration (Cmin) of BG-89894		Approximately up to 6 months
Phase 1b: Accumulation Ratio (AR) of BG-89894		Twice in the first month
Phase 1a: Overall response rate (ORR)	ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1.	Approximately 18 months
Phase 1a and 1b: Duration of response (DOR)	DOR is defined as the time from the first determination of objective response that is confirmed until the first documentation of disease progression or death, whichever comes first as assessed according to RECIST v1.1 by the investigator.	Approximately 18 months
Phase 1a and 1b: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with the best overall response of confirmed CR, PR, or stable disease as assessed according to RECIST v1.1 by the investigator.	Approximately 18 months
Phase 1b: Progression free survival (PFS)	PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of disease progression assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Approximately 18 months
Phase 1b: Number of particpants with AEs and SAEs	Number of participants experiencing adverse events and serious adverse events as determined per CTCAE v5.0, including findings from physical examinations, ECGs, and laboratory assessments as needed.	From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 24 months)
Phase 1b: Plasma Concentrations		Approximately up to 6 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2024
• Primary Completion (Actual): April 13, 2026
• Study Completion (Actual): April 13, 2026

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BG-89894-101; SYH2039-001 (Other Identifier: BeOne); CTR20242626 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No