Clinical trial NCT06568614: An Investigational Study of BG-89894 Tablets in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic MTAP-deleted Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
timeFrame: Approximately 1 month
measure: Phase 1a: Recommended dose(s) for expansion (RDFE) of BG-89894
timeFrame: Approximately 18 months
measure: Phase 1b: Recommended Phase 2 Dose (RP2D)
timeFrame: Approximately 18 months
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Approximately 18 months
Secondary outcomes:
measure: Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a and 1b: Apparent volume of distribution (Vd/F) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a and 1b: Apparent total clearance (CL/F) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a and 1b: Area under the concentration-time curve (AUC) for BG-89894
timeFrame: Twice in the first month
measure: Phase 1b: Minimum observed plasma concentration (Cmin) of BG-89894
timeFrame: Approximately up to 6 months
measure: Phase 1b: Accumulation Ratio (AR) of BG-89894
timeFrame: Twice in the first month
measure: Phase 1a: Overall response rate (ORR)
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Duration of response (DOR)
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Disease Control Rate (DCR)
timeFrame: Approximately 18 months
measure: Phase 1b: Progression free survival (PFS)
timeFrame: Approximately 18 months
measure: Phase 1b: Number of particpants with AEs and SAEs
timeFrame: 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)
measure: Phase 1b: Plasma Concentrations
timeFrame: Approximately up to 6 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital Huifu Branch
state: Guangdong
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: