Age between 18 and 70 years inclusive
Histologically or cytologically confirmed advanced malignant solid tumors, eligible patients have failed standard treatment, have no standard treatment, or are not suitable for standard treatment at this stage as determined by the investigator
Must have at least one evaluable lesion in dose escalation period and one unidimensional measurable lesion according to RECIST version 1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy 3 months
Adequate hematological and biological function, confirmed by the following laboratory values:ANC1.510^9/L;PLT7510^9/L;Hb90g/L;TBIL1.5ULN;AST and ALT3ULN(ALT and AST5ULN for subjects with liver cancer or hepatic metastases);CLcr>50 mL/min(according to Cockcroft-Gault);Child-Pugh score between 0~7 for subjects with primary hepatic carcinoma;APTT1.5ULN;INR1.5ULN
Men and women of childbearing potential are willing to employ an effective method of contraception for the entire duration of study and 6 months after the last dose, and female subjects of childbearing potential have a negative pregnancy test at baseline
Provision of signed and dated, written informed consent prior to any study-specific evaluation
Previous treatment with any TGF- inhibitors
Anticancer treatment including radiation therapy, chemotherapy, hormonal therapy, molecular targeted therapy, or immunotherapy within 4 weeks prior to the first dose of SH3051(use of mitomycin or nitrosoureas within 6 weeks prior to the first dose;use of oral oral fluorouracil and small molecule targeted drugs within 2 weeks ,or 5 half-lifes prior to the first dose;use of Chinese herbal anti-tumor treatment with 2 weeks prior to the first dose)
Have systematic hormonal therapy(prednisone>20mg/d or similar drugs with equivalent dose)or immunosuppressor therapy with 14 days prior to the first dose of study drug, except using topical,ocular,intra-articular,intranasal,inhaled corticosteroids,and preventive therapy using corticosteroids in short period(for instance,to prevent hypersensitivity to contrast media)
Participate in other clinical trials within 4 weeks prior to study entry
Concomitant use of any strong inhibitors or inducers of CYP3A4(except drug withdrawal within one week prior to first dose of study drug)
History of allogeneic hematopoietic stem cell transplantation or organ transplantation
Adverse events occurred during previous anticancer therapy have not been recovered to 1(CTCAE 5.0)except toxicity with no significant risk determined by investigators such as alopecia
Evidence of central nervous system (CNS) metastases accompanied with clinical symptoms, or other evidence of uncontrolled CNS metastases Judged by investigators that the patient should not participate in the study
Presence of grade 3 or 4 gastrointestinal bleeding or esophageal and gastric varices
Have moderate or severe cardiac disease, including but not limited to severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block,QTcF450 ms for male, QTcF470 ms for female, or other structural heart disease with high risk as determined by investigators;history of acute coronary syndrome, congestive heart failure,aortic dissection,stroke or othergrade 3 cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug;New York Heart Association (NYHA) Class II or greater heart failure, or LVEF<55%;cTnT or cTnI above the normal limit;NT-proBNP>1.25ULN;uncontrolled hypertension;any risk factors to increase QTc or arrhythmias, including heart failure,hypokalemia,congenital long QTc syndrome,family history of long QT interval syndrome or history of unexplained sudden death occurred in first degree relative less than 40 years of age, or using any concomitant medication known to produce QTc prolongation
Yes for Have moderate or severe cardiac disease, including but not limited to severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block,QTcF450 ms for male, QTcF470 ms for female, or other structural heart disease with high risk as determined by investigators;history of acute coronary syndrome, congestive heart failure,aortic dissection,stroke or othergrade 3 cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug;New York Heart Association (NYHA) Class II or greater heart failure, or LVEF<55%;cTnT or cTnI above the normal limit;NT-proBNP>1.25ULN;uncontrolled hypertension;any risk factors to increase QTc or arrhythmias, including heart failure,hypokalemia,congenital long QTc syndrome,family history of long QT interval syndrome or history of unexplained sudden death occurred in first degree relative less than 40 years of age, or using any concomitant medication known to produce QTc prolongation exclusion criteria 10
No for Have moderate or severe cardiac disease, including but not limited to severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block,QTcF450 ms for male, QTcF470 ms for female, or other structural heart disease with high risk as determined by investigators;history of acute coronary syndrome, congestive heart failure,aortic dissection,stroke or othergrade 3 cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug;New York Heart Association (NYHA) Class II or greater heart failure, or LVEF<55%;cTnT or cTnI above the normal limit;NT-proBNP>1.25ULN;uncontrolled hypertension;any risk factors to increase QTc or arrhythmias, including heart failure,hypokalemia,congenital long QTc syndrome,family history of long QT interval syndrome or history of unexplained sudden death occurred in first degree relative less than 40 years of age, or using any concomitant medication known to produce QTc prolongation exclusion criteria 10
Not sure for Have moderate or severe cardiac disease, including but not limited to severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block,QTcF450 ms for male, QTcF470 ms for female, or other structural heart disease with high risk as determined by investigators;history of acute coronary syndrome, congestive heart failure,aortic dissection,stroke or othergrade 3 cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug;New York Heart Association (NYHA) Class II or greater heart failure, or LVEF<55%;cTnT or cTnI above the normal limit;NT-proBNP>1.25ULN;uncontrolled hypertension;any risk factors to increase QTc or arrhythmias, including heart failure,hypokalemia,congenital long QTc syndrome,family history of long QT interval syndrome or history of unexplained sudden death occurred in first degree relative less than 40 years of age, or using any concomitant medication known to produce QTc prolongation exclusion criteria 10
Have active infection requiring systemic with one week prior to the first dose the study drug
Infection with hepatitis B virus(HBV)and hepatitis C virus(HCV) (volunteers with HBsAg positive but HBV-DNA negative, or volunteers with HCV antibody positive but HCV-RNA negative can be enrolled)
History of immune deficiency including HIV antibody positive
Major surgery(not include biopsy),or significant traumatism,or requiring selective operation within 4 weeks prior to study entry
Inability to swallow the drug, or severe gastrointestinal disease affecting absorption of the drug
Uncontrolled effusion in the third space, not suitable for entry as determined by the investigator
With alcohol or drug abuse disorder
With mental disorders or non-compliance
Women who are pregnancy or breastfeeding
Judgment by the investigator that the patient should not participate in the study