Advanced or Metastatic Solid Tumors With Homozygous MTAP DeletionPhase 1NCT07469982
A Phase I Study of SY-9453 in Patients With Advanced Solid Tumors
A Phase 1 study testing SY-9453 in people with Advanced or Metastatic Solid Tumors With Homozygous MTAP Deletion, run by Shouyao Holdings (Beijing) Co. LTD at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors With Homozygous MTAP Deletion
- What is being tested?
- SY-9453
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteChina
- Study dates
- 12 Mar 2026to Feb 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 4.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).
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- 5.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).
- 8.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.
Who cannot join
- 1. 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.
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- 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.
- 4.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).
- 5.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).
- 6.Dysphagia, or presence of a gastrointestinal disorder or other malabsorption condition that affects drug absorption, such as intestinal obstruction, Crohn's disease, ulcerative colitis, severe peptic ulcer, gastrointestinal perforation, or acute gastrointestinal bleeding.
- 7. Presence of active central nervous system (CNS) disease (if the clinical performance is stable assessed by the investigator at least 4 weeks before the first dose of SY-9453, and steroid treatment has been discontinued for ≥14 days, the patients can be included.
- 8.Hepatitis B during screening (positive results for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb] with HBV-DNA ≥1000 IU/mL; patients whose HBV-DNA levels drop to below 1000 IU/mL after regular antiviral treatment can be included), or active hepatitis C (HCV RNA > central detection upper limit of normal [ULN]), active syphilis (positive for both Treponema pallidum-specific and non-specific antibodies); history of tuberculosis (evidence of active tuberculosis infection within 1 year), Human immunodeficiency virus (HIV) positive during screening, or known history of other immunodeficiency diseases.
- 9.Presence of other underlying medical conditions as assessed by the investigator may put the subject at risk or affect the assessment of the toxicity of SY-9453 or AEs.
- 10. History of neurological or mental disorders, such as dementia. 11. Presence of the following clinically significant comorbidities, including but not limited to:
- .Left ventricular ejection fraction (LVEF) ≤ 50%.
- . Heart failure, myocardial infarction, unstable angina with 6 months, or classified as New York Heart Association (NYHA) class II, III or IV congestive heart failure.
- . High-risk uncontrolled arrhythmias within 6 months: atrial tachycardia with a resting heart rate >100 beats/min, significant ventricular arrhythmias (such as ventricular tachycardia), or high-grade atrioventricular block (such as type II second-degree or third-degree atrioventricular block).
- .History of Percutaneous Transluminal Coronary Angioplasty (PTCA) or stent implantation within 6 months.
- . Aortic stenosis.
- . Fridericia-corrected QT interval (QTcF) > 470 msec (females) or 450 msec (males) at baseline (if QTcF prolongation suspected to be drug-induced is assessed as safe and controllable by the investigator, the patient can be included after correction with medication).
- .Poorly controlled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110mmHg) or diabetes (fasting blood glucose ≥ 11.1mmol/L and/or HbA1c ≥ 8%).
- .Clinically significant active infection requiring systemic antibiotic, antiviral, or antifungal therapy.
- .Serous cavity effusion, or pleural effusion, ascites, or pericardial effusion poorly controlled after intervention (poorly controlled indicates significant increase in effusion within 2 weeks after drainage, with significant symptoms requiring re-puncture or other interventions).
- Stroke occurred within 6 months before screening. Evidence of central nervous system bleeding on baseline MRI or CT scan (subject had asymptomatic grade 1 bleeding stable for less than 3 months postoperatively).
- . Presence of drug-resistant seizures.
- .Severe lung diseases, including but not limited to pulmonary embolism, severe asthma, chronic obstructive pulmonary disease (COPD), restrictive lung disease, or active pneumonia or interstitial pneumonia that occurred 3 months before signing the notification, and pulmonary function tests indicate severe impairment of lung function.
- 12. History of allogeneic organ transplantation or allogeneic peripheral blood stem cell transplantation (allo-HSCT)/bone marrow transplantation.
- 13. Use of or inability to stop using the following CYP3A4 potent inhibitors or inducers within 2 weeks before the first dose during the study.
- 14. Pregnancy or breastfeeding women. 15. Other situations deemed unsuitable for participation in this clinical trial by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai East Hospital
Shanghai
caicun zhou, caicunzhoudr@163.com
About this study
Official title: An Open-label, Multi-center, Dose-escalation and Dose-expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SY-9453 in Patients With Advanced Solid Tumors
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.
Read the detailed description
The study will be conducted in 2 parts:
Dose-escalation phase: Participants will be allocated to one of the seven dose groups ranging from 5mg to 80mg and receive a single dose of SY-9453 capsules.This phase is designed to determine the DLTs (Dose-limiting toxicity) and recommended phase II dose (RP2D) and characterize the safety, tolerability and PK of SY-9453 in patients with advanced solid tumors.
Dose-expansion phase: Based on the recommended doses (RDEs) obtained in the escalation phase (possibly 1-2 doses), a dose expansion study will be conducted in 1-3 MTAP homozygous deletion advanced or metastatic solid tumor cohorts, with 10-20 patients per dose in each cohort to further evaluate the safety, tolerability, PK characteristics and anti-tumor activity of SY-9453 to clarify RP2D.
- Being tested
- SY-9453
- Keywords
- MTAP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SY-9453Drug
Also called SY-9453 capsules
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: SY-9453 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of adverse events (AEs)
Characterization of the safety and tolerability
Measured: Up to 3 years
Incidence of dose limiting toxicities (DLTs)
Characterization of the safety and tolerability
Measured: Escalation phase (35 days after the first dose)
Number of Participants With Abnormal Laboratory Values
Characterization of the safety and tolerability
Measured: up to 3 years
Recommended Phase II Doses (RP2D) of SY-9453
Measured: Up to 2 years
Maximum tolerated dose of SY-9453 (if applicable)
Characterization of the safety and tolerability
Measured: up to 1 year
Secondary outcomes (8)
Pharmacokinetics (Cmax) for SY-9453
Defined as maximum observed plasma concentration
Measured: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (Tmax) for SY-9453
Defined as time to maximum plasma concentration
Measured: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (AUC0-t) for SY-9453
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
Measured: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (t½) for SY-9453
Defined as the apparent plasma terminal phase disposition half-life
Measured: At the end of Cycle 1 (each cycle is 28 days)
Overall Response Rate (ORR) assessed by RECIST v1.1
Preliminary anti-tumor activity of SY-9453
Measured: Up to 3 years
Disease control rate (DCR) as assessed by RECIST v1.1
Preliminary anti-tumor activity of SY-9453
Measured: Up to 3 years
Duration of response (DOR) as assessed by RECIST v1.1
Preliminary anti-tumor activity of SY-9453
Measured: up to 3 years
Overall survival
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study start12 Mar 2026
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid Tumors With Homozygous MTAP DeletionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTD
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai East Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07469982
- Sponsor's protocol ID
- SY-9453-I-01
- Status last verified
- Apr 2026
- First submitted
- 3 Mar 2026
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center, Dose-escalation and Dose-expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SY-9453 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT07469982
- Acronym / sponsor ID
- SY-9453-I-01
- Keywords
- MTAP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTDUniversity, hospital or other
- Collaborators
- Shanghai East Hospital
- Study start
- 12 Mar 2026 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2029 (estimated)
- First posted
- 13 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will be conducted in 2 parts:
Dose-escalation phase: Participants will be allocated to one of the seven dose groups ranging from 5mg to 80mg and receive a single dose of SY-9453 capsules.This phase is designed to determine the DLTs (Dose-limiting toxicity) and recommended phase II dose (RP2D) and characterize the safety, tolerability and PK of SY-9453 in patients with advanced solid tumors.
Dose-expansion phase: Based on the recommended doses (RDEs) obtained in the escalation phase (possibly 1-2 doses), a dose expansion study will be conducted in 1-3 MTAP homozygous deletion advanced or metastatic solid tumor cohorts, with 10-20 patients per dose in each cohort to further evaluate the safety, tolerability, PK characteristics and anti-tumor activity of SY-9453 to clarify RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation and Dose-expansion | Experimental | Drug: SY-9453In 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- 4.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).
Key exclusion criteria (35 listed)
- 1. 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SY-9453Also: SY-9453 capsulesDose-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. | Drug | Dose-escalation and Dose-expansion |
Primary outcome
The incidence of adverse events (AEs)
Time frame: Up to 3 years
Characterization of the safety and tolerability
Incidence of dose limiting toxicities (DLTs)
Time frame: Escalation phase (35 days after the first dose)
Characterization of the safety and tolerability
Number of Participants With Abnormal Laboratory Values
Time frame: up to 3 years
Characterization of the safety and tolerability
Recommended Phase II Doses (RP2D) of SY-9453
Time frame: Up to 2 years
Maximum tolerated dose of SY-9453 (if applicable)
Time frame: up to 1 year
Characterization of the safety and tolerability
8 secondary outcomes
Pharmacokinetics (Cmax) for SY-9453
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (Tmax) for SY-9453
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (AUC0-t) for SY-9453
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Pharmacokinetics (t½) for SY-9453
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Overall Response Rate (ORR) assessed by RECIST v1.1
Time frame: Up to 3 years
Disease control rate (DCR) as assessed by RECIST v1.1
Time frame: Up to 3 years
Duration of response (DOR) as assessed by RECIST v1.1
Time frame: up to 3 years
Overall survival
Time frame: up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SY-9453 in people with Advanced or Metastatic Solid Tumors With Homozygous MTAP Deletion, run by Shouyao Holdings (Beijing) Co. LTD at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact chen guang wang (010-8885-8866, cgwang@centaurusbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of adverse events (AEs) (time frame: Up to 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.