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

NCT06568614 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: BG-89894-101SYH2039-001CTR20242626
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 20

Brief Summary

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.

Conditions

Advanced or Metastatic MTAP-deleted Solid Tumors

Outcome Measures

Primary Outcomes (5)

• 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: 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: 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 Outcomes (14)

• 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

Study Arms (2)

Phase 1a: Dose Escalation and Safety Expansion

EXPERIMENTAL

Sequential cohorts of increasing dose levels of BG-89894 (SYH2039) will be evaluated as monotherapy.

Drug: BG-89894

Phase 1b: Dose Expansion and Optimization

EXPERIMENTAL

Multiple indication-specific cohorts will be evaluated for safety, tolerability, and potential dose optimization of BG-89894 (SYH2039).

Drug: BG-89894

Interventions

BG-89894 DRUG

Administered orally

Also known as: SYH2039

Phase 1a: Dose Escalation and Safety Expansion; Phase 1b: Dose Expansion and Optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeOne Medicines: lead

Study Sites (20)

Sidney Kimmel Comprehensive Cancer At Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1010, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032-3725, United States

Location

Next Virginia

Fairfax, Virginia, 22031, United States

Location

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, NSW 2148, Australia

Location

Cancer Research South Australia

Adelaide, South Australia, SA 5000, Australia

Location

St Vincents Hospital

Fitzroy, Victoria, VIC 3065, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, WA 6009, Australia

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Beijing Tsinghua Changgung Hospital

Beijing, Beijing Municipality, 102218, China

Location

Guangdong Provincial Peoples Hospital Huifu Branch

Guangzhou, Guangdong, 510120, China

Location

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530021, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Hospital of China Medical University Hunnan Branch

Shenyang, Liaoning, 110167, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 23, 2024
• Study Start: October 12, 2024
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

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

Locations

AU (4); CN (12); US (4)