A Study Evaluating SYHX2005 in the Treatment of Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a first-in-human study with the SYHX2005 tablet primarily designed to evaluate the safety and tolerability of SYHX2005 at increasing doses in patients with advanced solid tumors and for whom no standard of care exists. The study will be conducted in two parts: Stage1 dose-escalation and Stage2 dose-expansion. In Stage1, patient enrolment will be proceeded according to a Accelerated Titration + BOIN design in order to identify the maximum-tolerated dose (MTD) or recommended dose. In Stage2, preliminary efficacy response will be assessed in patients with advanced solid tumors in use of the recommended dose.

Official Title
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Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SYHX2005 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SYHX2005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 70 years old (inclusive). Patients with advanced solid tumors diagnosed histologically or cytologically. Could provide tumor tissue sections or agree to take biopsy for central laboratory biomarker detection. At least one measurable lesion according to RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Life expectancy of at least 3 months. Adequate organ function. Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug. Female with child bearing potential must have had a negative serum pregnancy test and must be non-breastfeeding. Provide written informed consent voluntarily. Exclusion Criteria: Prior treatment with selective FGF19-FGFR4 inhibitor and / or treatment with Pan FGFR inhibitor. Received any anti-tumor treatment within 4 weeks before the first use of the study drug. Treatment with surgery, COVID-19 vaccine, or investigational drug within 4 weeks prior to the first study treatment administration. CYP3A4 strong inducer used within 14 days prior to the first administration or required during the study, or CYP3A4 strong inhibitor have used within 1 week before the first study treatment administration; or CYP3A4 strong inhibitor and P-gp, BCRP transporter strong inhibitor have to be used during the study. Patients with any ≥Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior anti-cancer therapy. Other malignant tumors requiring any active treatment at the same time. CNS metastases that are untreated or symptomatic or uncontrolled, so it is not suitable to be included in the group according to the judgment of the investigator. Pleural/peritoneal fluid or pericardial effusion with clinical signs or requiring symptomatic management. Active infection and need systemic anti infection treatment within 7 days before the first use of the study drug. History of autoimmune diseases and immunodeficiency, including HIV positive test, or have other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation. Active hepatitis B, hepatitis C virus infection. History of uncontrollable or serious cardiovascular and cerebrovascular diseases. Unable to swallow drugs orally, or there are conditions that seriously affect gastrointestinal absorption as judged by the investigator. Symptomatic irritable bowel syndrome and requires treatment. Known alcohol or drug dependence. Mental disorders or poor compliance. The investigator believes that the patients are not suitable for this clinical study due to other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: SYHX2005<br>Stage1 dose-escalation: Patients with advanced solid tumors will receive escalating doses of SYHX2005 as monotherapy. Stage2 dose-expansion: Patients with advanced solid tumors will receive SYHX2005 monotherapy at recommended dose (1 or 2 ) in Stage 1 (dose escalation) to evaluate the preliminary antitumor activity of SYHX2005. | Drug: SYHX2005<br>* Tablets. Take orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose(MTD) | Maximum tolerated dose | At the end of Cycle 1 (each cycle is 28 days) | 
| Overall Response Rate (ORR) in stage 2 | Overall Response Rate | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and frequency of adverse events (AE) and serious adverse events (SAE) | Rate of adverse events (AE) and serious adverse events (SAE) | 12 months | 
| Overall Response Rate (ORR) in stage 1 | Overall Response Rate | 12 months | 
| Duration of Response (DOR) | Duration of Response | 12 months | 
| Disease Control Rate (DCR) | Disease Control Rate | 12 months | 
| Progression-Free Survival (PFS) | Progression-free survival | 12 months | 
| Overall Survival (OS) | Overall Survival | 12 months | 
| Pharmacokinetic profile,e.g.AUC of SYHX2005 | Area Under the Plasma Concentration Versus Time Curve (AUC) | 12 months |