A First-in-human Study of HRS2398 Tablets in Subjects With Advanced Malignant Tumors

Inclusion criteria

• Subjects are able to give voluntary informed consent, understand the study and are willing to follow and complete all the test procedures.
• subjects ≥18 years and ≤70 years.
• Patients with Histologically or cytologically confirmed advanced Malignant tumors who had failed standard treatment or had not been treated with standard therapy.
• ECOG ≤1.
• Subjects with life expectancy of ≥ 3 months.
• At least one measurable lesion ( RECIST version 1.1).
• Subjects must have adequate organ function (whole blood or component transfusion or BFGF within 2 weeks before 1st dose of study drug is prohibited):

• Absolute neutrophil count (ANC) ≥1.5 x10^9/L;
• Platelet count ≥ 100 x 10^9/L;
• Hemoglobin ≥ 90 g / L;
• Total bilirubin (TBil) ≤1.5 x ULN;
• Liver function tests alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN, for patients with known liver cancer or liver metastases, AST and ALT ≤ 5 x ULN;
• Gr ≤ 1.5x ULN or an estimated glomerular filtration rate (eGFR) > 50 mL/min;
• INR ≤1.5 x ULN and APTT ≤ 1.5 x ULN;
• LVEF≥50%，QTc Male: <450ms; Female: <470ms.
• Subjects (males and females) of childbearing potential should be willing to use reliable contraception methods that are deemed effective by the investigator from visit 1 through 180 days following the last dose of study drug.
• Archived wax lump tumor tissue samples or biopsy and blood sample collection during screening period.
• As judged by the investigator, can follow protocol.

Exclusion criteria

• Untreated and/or uncontrolled brain metastases.
• Patients with clinical symptoms of cancer ascites, pleural effusion, who need to drainage, or who have undergone ascites drainage within 2 weeks prior to the first administration.
• Failure to recover from adverse events from the most recent anti-tumor treatment to CTCAE ≤ grade2.
• Inability to swallow tablets or gastrointestinal disease, possible impairment of adequate absorption of study drugs.
• Have severe cardiac disease:NYHA class ≥grade II heart failure; unstable angina pectoris；myocardial infarction within 12 months； clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; Hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
• Known active hepatitis C virus, or known active hepatitis B virus.
• Allergic to the HRS2398 or the similar drug.
• Concurrent anticancer treatment or use of other investigational product within 4 weeks before start of trial treatment; major surgery, radiotherapy, chemotherapy within 4 weeks before 1st dose of trial treatment.
• The patient is currently using a drug known to be a strong inhibitor of CYP3A4 within 2 weeks before 1st dose of study drug ，or strong inducer of CYP3A4 within 4 weeks before 1st dose of study drug .
• The investigator determined that the patient should not participate in the study.