A Phase I Study of SY-9453 in Patients With Advanced Solid Tumors

NCT07469982 | Recruiting Phase 1

• 1 other identifier: SY-9453-I-01
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, multicenter, dose-escalation and dose-expansion, phase I study to the safety, tolerability, pharmacokinetics, and preliminary efficacy of SY-9453 in patients with advanced solid tumors.

Conditions

Advanced or Metastatic Solid Tumors With Homozygous MTAP Deletion

Keywords

MTAP

Outcome Measures

Primary Outcomes (5)

• The incidence of adverse events (AEs)

  Characterization of the safety and tolerability

  Up to 3 years

• Incidence of dose limiting toxicities (DLTs)

  Characterization of the safety and tolerability

  Escalation phase (35 days after the first dose)

• Number of Participants With Abnormal Laboratory Values

  Characterization of the safety and tolerability

  up to 3 years

• Recommended Phase II Doses (RP2D) of SY-9453

  Up to 2 years

• Maximum tolerated dose of SY-9453 (if applicable)

  Characterization of the safety and tolerability

  up to 1 year

Secondary Outcomes (8)

• Pharmacokinetics (Cmax) for SY-9453

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics (Tmax) for SY-9453

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics (AUC0-t) for SY-9453

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics (t½) for SY-9453

  At the end of Cycle 1 (each cycle is 28 days)

• Overall Response Rate (ORR) assessed by RECIST v1.1

  Up to 3 years

Other Outcomes (4)

• Changes in serum symmetric dimethylarginine (SDMA) from baseline

  up to 3 years

• Changes in ctDNA from baseline

  up to 3 years

• The incidence of adverse events related to QTcF prolongation

  At the end of Cycle 1 (each cycle is 28 days)

Study Arms (1)

Dose-escalation and Dose-expansion

EXPERIMENTAL

In dose-escalation phase, SY-9453 will be given orally in ascending doses (escalation cohort) until the DLT or Recommended doses（RDEs) is reached. In dose-expansion phase, SY-9453 will be given orally in RDEs (possibly 1-2 doses) for the expansion period based on the escalation phase in 28-day cycle continuously.

Drug: SY-9453

Interventions

SY-9453 DRUG

Dose-escalation phase: Multiple doses of SY-9453 for oral administration ranging from 5mg to 80mg. Dose-expansion phase: RDEs of SY-5007 asdetermined during Dose Escalation.

Also known as: SY-9453 capsules

Dose-escalation and Dose-expansion

Eligibility Criteria

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

You may qualify if:

• Patients must meet all of the following criteria to be eligible for this study:
• Subjects voluntarily participated in this study and signed the written informed consent (ICF);
• Age ≥ 18 years at the time of signing the Informed Consent Form (ICF);
• Histologically or cytologically confirmed locally advanced solid tumor and disease progression or intolerance after adequate standard treatment, or lack of standard treatment options.
• For subjects participating in the dose escalation phase (only for dose groups of 30 mg and above) and the dose expansion phase: be able to provide a previous test report confirmed by NGS or IHC to be homozygous deletion of the MTAP gene approved by the investigator, or agree to provide sufficient archived or baseline tumor tissue samples, confirmed to be homozygous deletion of the MTAP gene by central laboratory testing.
• At least one measurable extracranial lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 criteria or mRECIST V1.1（Mesothelioma subjects only）(subjects participating in accelerated titration phase are not required to meet this requirement).
• Expected survival of \>3 months. 6.Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. 7.Organ function levels must meet the following requirements:
• No blood products, hematopoietic growth factors (e.g., G-CSF, thrombopoietin, erythropoietin, platelet transfusion, whole blood transfusion, red blood cell transfusion), or other drugs that correct abnormal blood counts for at 14 days before first dosing and the following blood counts: ANC ≥ 1.5 × 10\^9/L, PLT count ≥ 100 × 10\^9/L, Hb ≥ 90 g/L.
• Renal function: Creatinine clearance (Ccr) ≥ 60 mL/min (calculated using the Cockcroft and Gault formula).
• Liver function: TBIL ≤ 1.5 × upper limit of normal (ULN), and AST and ALT ≤ 2.5 × ULN; in the presence of liver metastases, AST and ALT ≤ 5.0 × ULN, and serum albumin ≥ 30 g/L.
• Coagulation function: Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN, and International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN (except for patients receiving anticoagulant therapy).
• Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the first dose, male and female patients of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception during the entire study duration and for at least 3 months after the last dose of study medication.

You may not qualify if:

• \. Patients previously treated with a MAT2A inhibitor or PRMT5 inhibitor. 2. History of allergy to any component or excipient of SY-9453 capsules. 3. Received the following treatments prior to the first dose:
• Small-molecule targeted drugs within 2 weeks(or 5 half-lives, whichever is shorter).
• Hormonal anti-tumor therapy within 2 weeks or as judged by the investigator.
• Chinese herbal medicine or preparations with indications for anti-tumor therapy or tumor adjuvant therapy within 2 weeks or as judged by the investigator.
• Radiotherapy within 4 weeks (with 2 weeks if the radiotherapy was palliative stereotactic radiotherapy that did not involve the lungs, abdomen and pelvis)
• Chemotherapy: fluorouracil, leucovorin, and/or weekly paclitaxel with 2 weeks; nitrosourea or mitomycin C with 6 weeks; other chemotherapy with 3 weeks.
• Other investigational drugs with 4 weeks.
• Biotherapy within 4 weeks(or 5 half-lives, whichever is longer)
• Immunotherapy within 4 weeks.
• Major surgery within 4 weeks (excluding central venous catheter insertion, bone marrow biopsy and gastric tube insertion).
• Radioactive Particle Therapy within 3 months.
• Radionuclide therapy within 3 months.
• Autotransplantation (including CAR-T therapy and other similar treatments) within 3 months.
• Adverse events from prior anti-cancer therapies have not recovered to Grade ≤1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 (except for toxicities assessed by the investigator as posing no safety risk, such as alopecia and Grade 2 peripheral neuropathy).
• Other malignancies within 3 years before screening, with the following exceptions: cured cervical carcinoma in situ, squamous cell carcinoma of the skin, and cured basal cell carcinoma(except for the subjects participating in accelerated titration phase).

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead
• Shanghai East Hospital: collaborator

Study Sites (1)

Shanghai East Hospital

Shanghai, China

RECRUITING

Central Study Contacts

chen guang wang

CONTACT

010-8885-8866; cgwang@centaurusbio.com

Study Design

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

Study Record Dates

• First Submitted: March 3, 2026
• First Posted: March 13, 2026
• Study Start: March 12, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

CN (1)