This is a multi-center, open-label, dose escalation and expansion, phase I study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) characteristics, preliminary efficacy of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors. Once the expected effective dose is identified, the dose expansion study will be started to further evaluate the safety, clinical activity and PK profile of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors.
This is a multi-center, open-label, dose escalation and expansion, phase I study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) characteristics, preliminary efficacy of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors. The dose escalation study will include six dose cohorts starting at 2 mg/day. Once the expected effective dose is identified, the dose expansion study will be started to further evaluate the safety, clinical activity and PK profile of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
97
Subjects will receive SYHA1815 orally.
Jilin Cancer Hospital
Changchun, Jilin, China
RECRUITINGNumber of participants with Dose-limiting Toxicities
Number of participants with Dose-limiting Toxicities
Time frame: Baseline through 28 days after the first dose of study drug
Incidence of adverse events and SAEs
Incidence of adverse events and SAEs defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0).
Time frame: Up to 3 years
Clinically significant changes from baseline in routine blood test
Clinically significant changes from baseline in routine blood test
Time frame: Up to 3 years
Clinically significant changes from baseline in blood biochemistry test
Clinically significant changes from baseline in blood biochemistry test
Time frame: Up to 3 years
Clinically significant changes from baseline in routine urine test
Clinically significant changes from baseline in routine urine test
Time frame: Up to 3 years
Clinically significant changes from baseline in coagulation function test
Clinically significant changes from baseline in coagulation function test
Time frame: Up to 3 years
Clinically significant changes from baseline in 12-lead electrocardiogram (ECG)
Clinically significant changes from baseline in 12-lead electrocardiogram (ECG)
Time frame: Up to 3 years
Clinically significant changes from baseline in vital signs examination
Clinically significant changes from baseline in vital signs examination
Time frame: Up to 3 years
Clinically significant changes from baseline in physical examination
Clinically significant changes from baseline in physical examination
Time frame: Up to 3 years
Objective Response Rate (ORR)
Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1
Time frame: Up to 3 years
Disease control rate (DCR)
Disease control rate (DCR)
Time frame: Up to 3 years
Duration of response (DOR)
Duration of response (DOR)
Time frame: Up to 3 years
Progression free survival (PFS)
Progression free survival (PFS)
Time frame: Up to 3 years
Time to maximum plasma concentration (Tmax)
Time to maximum plasma concentration (Tmax)
Time frame: Up to 3 years
Maximum Plasma Concentration (Cmax)
Maximum Plasma Concentration (Cmax)
Time frame: Up to 3 years
Plasma half-life (T1/2)
Plasma half-life (T1/2)
Time frame: Up to 3 years
Area under the plasma concentration-time curve from time 0 to time t (AUC0-t)
Area under the plasma concentration-time curve from time 0 to time t (AUC0-t)
Time frame: Up to 3 years
Area under the plasma concentration-time curve from time 0 to infinity (AUCinf)
Area under the plasma concentration-time curve from time 0 to infinity (AUCinf)
Time frame: Up to 3 years
Terminal disposition rate constant (λz)
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Terminal disposition rate constant (λz)
Time frame: Up to 3 years
Apparent total clearance of the drug from plasma after oral administration (CL/F)
Apparent total clearance of the drug from plasma after oral administration (CL/F)
Time frame: Up to 3 years
Apparent volume of distribution during terminal phase after non-intravenous administration (Vz/F)
Apparent volume of distribution during terminal phase after non-intravenous administration (Vz/F)
Time frame: Up to 3 years
Change from baseline in serum phosphate
Change from baseline in serum phosphate
Time frame: Up to 3 years
Serum carcinoembryonic antigen (CEA)
Serum carcinoembryonic antigen (CEA)
Time frame: Up to 3 years
Calcitonin (thyroid cancer detection only)
Calcitonin (thyroid cancer detection only)
Time frame: Up to 3 years
Fibroblast growth factor 23 (FGF23)
Fibroblast growth factor 23 (FGF23)
Time frame: Up to 3 years
Vascular endothelial growth factor receptor 2 (sVEGFR2)
Vascular endothelial growth factor receptor 2 (sVEGFR2)
Time frame: Up to 3 years
Potential population who benefit from the study drug
To evaluate the efficacy of the study drug in patients with different indications according to the results of anti-tumor response rate in the corresponding indications.
Time frame: Up to 3 years
Correlation between the changes of RET/FGFR gene and efficacy
The percentage of patients with RET/FGFR gene in patients who benefit from the study drug will be assessed.
Time frame: Up to 3 years