NCT07692776尚未招募不适用
An Open-Label, Multi-Center Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SYH2095 in Advanced Malignant Tumors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.1 个研究点 分布在 1 个国家目标入组 140 人开始时间: 2026年7月1日最近更新:
适应症
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicity
研究概览
简要总结
This is an open-label, multicenter Phase 1 first-in-human trial of SYH2095, a selective KAT6A/B inhibitor. The trail contains two segments: Part 1A dose escalation and Part 2A cohort expansion. Part 1A uses the BOIN dose-escalation design, enrolling patients with advanced malignant tumors with no effective standard treatment. Its primary goals are to assess safety and tolerability, define dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), and establish the recommended expansion dose (RDE). Part 2A is an expansion cohort using the RDE identified in Part 1A,. All participants receive oral SYH2095 once daily in 4-week treatment cycles. Safety evaluations, tumor imaging, pharmacokinetic (PK), pharmacodynamic (PD) and biomarker analyses will be performed at scheduled time points throughout treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully understand this clinical trial, and voluntarily sign a written informed consent form (ICF);
- •Age ≥ 18 years (at the time of informed consent), male or female;
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score 0-1;
- •Estimated life expectancy ≥ 3 months;
- •At least one measurable or evaluable tumor lesion at baseline per RECIST V1.1;
- •For advanced HR+/HER2- breast cancer, the following requirements must be met:
- •HR positive is defined as: ER positive and/or PR positive, confirmed by tumor biopsy (biopsy method comply with local diagnosis and treatment standards) that the tumor tissue is ER/PR positive, and the proportion of positive staining cells among all tumor cells is ≥1%;
- •HER2 negative is defined based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as: immunohistochemistry score of 0/1+, or a negative result determined by in situ hybridization (HER2/CEP17 ratio <2.0, or HER2 gene copy number <4.0 using a single probe);
- •Participants need to be postmenopausal. Female participants with childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause by treatment with the approved LHRH agonist such as goserelin, leuprolide, or an equivalent to induce chemical menopause.7.Participants with childbearing potential (male or female) must agree to use a reliable contraceptive method (see Appendix 13.1) with their partner during trial and for at least 13 weeks (males) or 25 weeks (females) after the last dose. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose;
- •8.Participants must meet the following laboratory tests requirements (all test results must be completed within 7 days before the first dose without corrective interventions such as transfusion, hematopoietic growth factors, etc., or stable for more than 7 days after treatment)
排除标准
- •Presence of known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Participants with prior locoregional treatment for brain metastases may be enrolled only if medically stable for ≥ 4 weeks prior to the first dose. Medically stable is defined as the following conditions: no clinical symptoms attributable to CNS metastases within 4 weeks prior to the first dose (e.g., progressive or new neurological deficit, epileptic seizure, increased intracranial pressure, vomiting, papilledema, or headache); no evidence of CNS neoplasm relapse/progression on imaging assessments within 4 weeks prior to the first dose; no glucocorticoid therapy (>10 mg/day prednisone or equivalent) for ≥4 weeks prior to the first dose;
- •Participants with uncontrolled third interstitial effusions (e.g., pericardial effusion, pleural effusion, ascites) that cannot be controlled by repeated drainage or other interventions, and who are not suitable for enrollment by the investigator;
- •Participants with history of severe cardiovascular disease within 6 months prior to the first dose, including any of the following: (1) Congestive heart failure (New York Heart Association (NYHA) class > grade Ⅱ); (2) Severe/unstable angina, or new-onset angina pectoris within 3 months before the first dose; (3) Participants with myocardial ischaemia requiring long-term pharmacologic control, or heart failure (NYHA class Ⅲ-Ⅳ); (4) History of acute myocardial infarction; (5) Any grade ≥2 supraventricular or ventricular arrhythmia requiring treatment or intervention; (6) History of atrial fibrillation, coronary/peripheral artery bypass grafting, or transient ischaemic attack (TIA) with cerebrovascular symptoms; (7) Uncontrolled hypertension at screening (despite pharmacotherapy: diastolic blood pressure ≥ 100 mmHg and/or systolic blood pressure ≥ 160 mmHg);(8) QTcF≥ 470 ms on 12-lead (ECGs) performed in triplicate;
- •Participants with factors affecting oral administration (e.g., dysphagia, intestinal obstruction); or active gastrointestinal diseases or other conditions that may significantly alter drug absorption, distribution, metabolism, or excretion (including active inflammatory bowel disease, chronic diarrhea, frequent vomiting, enterocolitis, etc.);
- •Participants with active autoimmune disease, a history of immunodeficiency or autoimmune disease, or a history of non-active autoimmune disease requiring long-term treatment with systemic corticosteroids or immunosuppressants agents, or with conditions associated with immunodeficiency (including HIV, congenital immunodeficiency diseases, etc.), or a history of organ transplantation (including allogeneic bone marrow transplantation);
- •Drug-induced pneumonia, interstitial lung disease (ILD), or immune-mediated pneumonitis; or a history of active radiation pneumonitis requiring steroid therapy, or other severe lung dysfunction diseases, symptoms or signs at screening (e.g., severe chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, etc.);
- •Presence of active hepatitis B, active hepatitis C, active tuberculosis, or active syphilis infection, including:
- •A. Active hepatitis B: HBsAg positive and HBV-DNA quantitative titer test ≥20 IU/mL or HBV-DNA ≥102; B. Active Hepatitis C: anti-HCV positive and HCV-RNA positive; C. Active tuberculosis: history of tuberculosis treatment within 2 years prior to the first dose; D. Active syphilis: presence of syphilis infection requiring systemic therapy;
- •Participants with a diagnosis of other malignant tumor within the past 5 years (except those with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, papillary thyroid carcinoma, or carcinoma in situ [e.g., cervical carcinoma in situ, breast ductal carcinoma in situ] that have received radical treatment);
- •Use of strong/moderate inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose;
- •Use of proton pump inhibitors (PPIs) within 2 weeks prior to the first dose;
- •History of nervous system or psychiatric disorders, history of psychotropic drug abuse, or drug addiction ; alcohol or drug abuse/dependence, which may interfere with the administration of the investigational product, affect the assessment and judgment of investigational product's toxicity and AEs, or result in inadequate or decreased trial compliance; participants with other severe physical or laboratory abnormalities that, in the investigator's judgment, may increase the risk to the participant or interfere with the clinical trial results, and are thus considered unsuitable for trial participation;
- •Received any anti-tumor therapy or enrolled in other interventional clinical trial within 4 weeks prior to the first dose, including cytotoxic drugs, endocrine therapy, immunotherapy, targeted therapy, surgery (except puncture biopsy, peripherally inserted central catheterisation or infusion port catheterization) or other clinical trial investigational products; or received radiotherapy within 2 weeks prior to the first dose;
- •Previous anti-tumor therapy-related toxicity that has not recovered to CTCAE version 6.0 grade ≤1 (except toxicities determined by the investigator to post no safety risk, e.g., alopecia, fatigue, isolated laboratory abnormalities, peripheral neuropathy, etc.);
- •Previous participation in any clinical trial involving a KAT6A/B or KAT7 inhibitor;
- •Hypersensitivity to any investigational product or its excipients in this clinical trial;
- •Female participants who are pregnant, breastfeeding, or planning a pregnancy during the trial;
- •Participants with active infection requiring treatment with antibiotics, antivirals or antifungals, or unexplained fever >38.5℃ within 2 weeks prior to the first dose (except tumor-related fever as determined by the investigator);
- •Participants with hemorrhagic events within 4 weeks prior to the first dose (e.g., active gastrointestinal bleeding, gross hematuria, haemoptysis, etc.);
- •Presence of severe bone injury due to bone metastases, as determined by the investigator, including uncontrolled severe bone pain, pathological fractures at critical sites, or spinal cord compression that occurred within 6 months prior to the first dose or is expected to occur in the near future;
结局指标
主要结局
Incidence of Dose-Limiting Toxicity
时间窗: End of Part 1 Dose Escalation and Backfill phase (each cycle is 28 days; all safety data collected through Day 28 of Cycle 1 for every dose-escalation subject)]
Proportion of participants with DLT during the first 28-day treatment cycle (DLT observation period), assessed per NCI-CTCAE 6.0.
Maximum Tolerated Dose (MTD) of SYH2095
时间窗: End of Part 1 Dose Escalation and Backfill phase (each cycle is 28 days; all safety data collected through Day 28 of Cycle 1 for every dose-escalation subject)]
Determine the MTD of SYH2095 for monotherapy based on DLT and overall safety data.
Maximum Tolerated Dose of SYH2095
时间窗: End of Part 1 Dose Escalation phase (each cycle is 28 days; safety data collected through Day 28 of Cycle 1 for all dose-escalation subjects)]
Description: Determine the MTD of SYH2095 for monotherapy based on DLT and overall safety data
Objective Response Rate
时间窗: 2 years
Confirmed ORR assessed by investigators per RECIST 1.1 in cohort expansion participants.
Phase 2 Recommended Dose of SYH2095
时间窗: 2 years
Determine RP2D for monotherapy based on safety, PK and efficacy data.
Overall Safety Profile
时间窗: From informed consent to 28 days after last study drug administration
Incidence, severity and causality of adverse event
Maximum Observed Concentration (Cmax)
时间窗: 2 years
Pharmacokinetic (PK) assessments for SYH2095 Part 1A and Part 2A
次要结局
- Disease Control Rate (DCR)(2years)
- Time to Maximum concentration (Tmax)(2 years)
- AUC from time zero to time of last measurable concentration (AUClast)(2 years)
- Terminal Elimination half-life (t1/2)(2 years)
- Steady-State Cmax(2 years)
- Steady-state Tmax (Tmax,ss)(2 years)
- Steady state AUC during a dosage interval (τ) (AUCτ,ss)(2 years)
- Steady-state apparent total clearance (CLss/F)(2 years)
- Progression Free Survival (PFS)(2 years)
- Overall survival (OS)(2 years)
- Duration of Response (DOR)(2 years)
研究者
研究点 (1)
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