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
Overview
- Phase
- Phase 1
- Intervention
- BG-89894
- Conditions
- Advanced or Metastatic MTAP-deleted Solid Tumors
- Sponsor
- BeOne Medicines
- Enrollment
- 140
- Locations
- 20
- Primary Endpoint
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
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.
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.
Arms & Interventions
Phase 1a: Dose Escalation and Safety Expansion
Sequential cohorts of increasing dose levels of BG-89894 (SYH2039) will be evaluated as monotherapy.
Intervention: BG-89894
Phase 1b: Dose Expansion and Optimization
Multiple indication-specific cohorts will be evaluated for safety, tolerability, and potential dose optimization of BG-89894 (SYH2039).
Intervention: BG-89894
Outcomes
Primary Outcomes
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 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)
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.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
Time Frame: 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) of BG-89894
Time Frame: Approximately 18 months
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.
Phase 1b: Overall Response Rate (ORR)
Time Frame: Approximately 18 months
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.
Phase 1b: Recommended Phase 2 Dose (RP2D)
Time Frame: Approximately 18 months
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.
Secondary Outcomes
- 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 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: Apparent terminal elimination half-life (t1/2) 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 1a and 1b: Maximum observed plasma concentration (Cmax) of 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)(Approximately 18 months)
- Phase 1a and 1b: Duration of response (DOR)(Approximately 18 months)
- Phase 1a and 1b: Disease Control Rate (DCR)(Approximately 18 months)
- Phase 1b: Progression free survival (PFS)(Approximately 18 months)
- Phase 1b: Number of particpants with AEs and SAEs(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)