To Evaluate the Safety and Tolerability of SYHX2001 in Patients With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multicenter, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the experimental drug(SYHX2001) in previously treated patients with advanced or metastatic cancer.

Detailed Description
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This is a multicenter, open-label, dose-escalation, dose-expansion Phase 1 study of SYHX2001(name of the experimental drug) in patients with advanced or metastatic cancers who have exhausted standard treatment. The study will consist of 2 parts, a dose escalation part and a cohort expansion part. Once the recommended phase 2 dose (RP2D) has been determined in the dose escalation part, a cohort expansion part involving up to three separate cohorts will be conducted. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of SYHX2001.

Official Title
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To Evaluate the Safety and Tolerability of SYHX2001 in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: SYHX2001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients with an age of 18 75years (inclusive). Confirmed histologic or cytologic diagnosis of an advanced and/or metastatic solid tumor. At least one measurable lesion as defined by RECIST version 1.1. Eastern Cooperative Oncology Group Performance Status 0 or 1. Life expectancy ≥3 months. Major organ function within 14 days prior to treatment meets the following criteria (no blood transfusion, Erythropoietin(EPO), Granulocyte Colony Stimulating Factor(G-CSF) or other medical support): Absolute Neutrophil Count(ANC)≥1.5×10^9/L，Platelet(PLT)≥90×10^9/L，Hemoglobin(Hb)≥100g/L or≥6.2 mmol/L；Creatinine(Cr)≤1.5×upper limit of normal(ULN) and creatinine clearance rate≥50mL/min；Total Bilirubin(TBIL)≤1.5×ULN; Prothrombin time(PT)≤1.5×ULN , Activated Partial Thromboplastin Time(APTT)≤1.5×ULN , Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT)≤2.5 × ULN. Signed informed consent form. Exclusion Criteria: Chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks prior to the first dose of the study drug, or administration of other investigational agents within 4 weeks or 5 half-lives prior to the first dose of the study drug, whichever is longer. Major surgery or significant trauma within 4 weeks prior to the first dose of the study drug. Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤ level 1 based on CTCAE 5.0。 Have a history of severe cardiovascular and cerebrovascular disease. Central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence shows that the patient's central nervous system metastasis or meningeal metastasis has not been controlled and not suitable for the study according to the judgment of the investigator. Known history of hypersensitivity to test drug components. Patients with recent active bleeding or a history of bleeding. Those with coagulation disorders or taking thrombolytic, anticoagulant or antiplatelet agglutination drugs. Gastrointestinal perforation, abdominal fistula, or intra-abdominal abscess within 6 months prior to first dose; or currently under investigator's judgement there are high risk factors for hollow organ perforation/fistula formation). Inability to swallow the drug orally, or a condition that seriously affects gastrointestinal absorption in the judgment of the investigator. Irritable bowel syndrome with signs/symptoms requiring medication. Persistent active diarrhea requiring medical treatment. Concomitant use of strong CYP3A4 inhibitors or inducers, strong CYP2D6 inhibitors and strong P-gp inhibitors within 14 days prior to the first dose of the study drug. History of autoimmune diseases, immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency, or organ transplant history. Known Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or other active viral infection. Male and female patients of childbearing potential do not agree to use suitable method of contraception during the treatment and 6 months after the last dose of study medication; female patients do not have negative results of serum/urine pregnancy test within 7 days prior to enrollment and would be breastfeeding. Not suitable for this study as determined by the investigator due to other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYHX2001<br>SYHX2001 will be administered orally. | Drug: SYHX2001<br>* SYHX2001 tablets, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLT) in stage Ⅰ |  | Baseline through Day 28 | 
| Maximum tolerated dose (MTD) in stage Ⅰ |  | Baseline through Day 28 | 
| Recommended phase 2 dose (RP2D) |  | Baseline through approximately 2 years | 
| Incidence and severity of adverse events in stage Ⅰ |  | Baseline through approximately 2 years | 
| Overall response rate (ORR) in stage Ⅱ |  | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of SYHX2001 |  | Baseline and up to approximately 2 years | 
| Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of SYHX2001 |  | up to approximately 2 years | 
| AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of SYHX2001 |  | up to approximately 2 years | 
| Terminal phase half-life (t1/2) of SYHX2001 |  | up to approximately 2 years | 
| Oral clearance (CL/F) of SYHX2001 |  | up to approximately 2 years | 
| PFS Progression-free survival (PFS) | PFS is defined as the time from first dose until radiographic progression per standard criteria or death due to any cause, whichever is earlier. | up to approximately 2 years | 
| Duration of Response (DOR) | DOR is defined as the time from first evidence of response (complete response or partial response per RECIST 1.1) to earlier date of disease progression or death due to any cause. | up to approximately 2 years | 
| Number of patients with any adverse events(AEs) and serious adverse events(SAEs) in stage Ⅱ |  | up to approximately 2 years | 
| Change from Baseline in symmetrical arginine dimethylation (SDMA) as a pharmacodynamics(PD) measure |  | Baseline and up to approximately 2 years |