Study of FCN-098 in Patients With Advanced Solid Tumor

Inclusion Criteria:

• 1. Age ≥ 18 years，no gender limitation；
• 2. Patients with inoperable solid tumors, stage III or IV, confirmed histologically orcytologically by standard treatment failure or no standard treatment;
• 3. Dose-escalation stage: patients with advanced solid malignancies after failure ofstandard treatment (patients with positive NTRK gene fusion or mutations in the TRKkinase region are preferred); Dose expansion stage: patients with advanced solidmalignant tumors with NTRK gene fusion positive or TRK kinase region mutation afterstandard treatment failure; NTRK gene fusion positive or TRK kinase region mutationcan be included based on the positive report of the local laboratory, but tissues mustbe provided to the central laboratory for confirmation;
• 4. The ECOG Scores 0 or 1 for physical fitness (Dose-escalation stage),0-2(Doseexpansion stage);
• 5. Can understand and be willing to sign informed consent prior to the commencement ofany research procedure;
• 6. Expected survival at least 12 weeks;
• 7. Patients with adequate organ and bone marrow function: absolute value ofneutrophils ≥ 1.0 × 10^9/L (no G-CSF treatment within 7 days);Hemoglobin ≥ 80g/L (noerythrocyte infusion within 7 days);Platelet ≥ 75 × 10^9/L; Serum total bilirubin ≤ 1.5 × upper limit normal (ULN), and patients with Gilbert syndrome ≤3.0 × ULN.Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN; Forpatients with liver metastasis, AST and ALT should be ≤ 5 × ULN. Creatinine<1.5×ULN orCreatinine clearance was ≥ 60 ml/min in dose-escalation stage, and ≥ 45ml/min in doseexpansion stage. Creatinine clearance was calculated by Cockroft - Gault formula.Albumin ≥ 3g/dL;
• 8. At least one evaluable lesion (Dose escalation stage) was assessed according toRECIST 1.1 or RANO criteria; According to RECIST 1.1 or RANO standard to evaluate, atleast one measurable lesions (Dose expansion stage) (primary central nervous systemtumors according to the standard definition RANO, needs to have one or more measurablelesions by MRI assessment, size for at least 10 mm or more, and appeared in two ormore ≤ 5 mm thick section, the measure does not include cystic cavity.) The imagingevaluation should be completed within 28 days before enrollment, and the patient'shormone dosage should be stable for at least 5 days or more.
• 9. A fertile woman must have a negative serum pregnancy test within 28 days of thefirst study drug administration and agree to contraception between 28 days before thefirst study drug administration and 90 days after the last study drug administration;Male patients are required to undergo ligation or agree to contraception and refusesperm donation from 7 days before the first dose to 30 days after the last dose; Thefailure rate of contraceptive methods<1% per year, such as double screen contraceptivemethods, condoms, oral or injectable contraceptives.

Exclusion Criteria:

• 1. Patients who received targeted therapy or tyrosine kinase inhibitor therapy within 2 weeks or within 5 half-lives (whichever is shorter) before starting administration,and who received chemotherapy, major surgery, radiotherapy, Anti-tumorbiopharmaceutical treatment, immunotherapy or clinical trials within 4 weeks or within 5 half-lives (which is shorter);
• 2. Uncontrolled or symptomatic brain metastases (asymptomatic or stably controlled CNSmetastases and no hormone therapy within 2 weeks are allowed to be enrolled);Patientswith spinal cord metastasis with symptoms of spinal cord compression;Primary CNStumors were allowed to be enrolled.
• 3. The toxicity of previous anti-tumor therapy has not recovered (>NCI-CITCAE 5.0level 2), neurotoxic reaction level 2, except hair loss;
• 4. Patients should use strong CYP3A4 inhibitors (except drugs permitted in Section 6.8), inducers or sensitive substrates and sensitive substrates of CYP2B6, CYP2C8,CYP2C6 at the same time;
• 5. Patients take drugs (mainly Ia, Ic, class III anti-arrhythmia drugs) that willprolong the QTc interval or have risk factors for extending the QTc interval;
• 6. Difficulty in swallowing, or having an absorbance syndrome, or other medicalconditions that prevent the absorption of drugs through the intestinal tract, oraffect the absorption of FCN-098;
• 7. Cardiac function and disease meet one of the following conditions:

1. screening period in research center 3 times of 12 lead ECG measurement, accordingto the instrument of QTc formula for calculating the average three times, QTc>470ms for female and QTc>450 ms for male.
2. continue uncontrolled hypertension, systolic blood pressure underantihypertensive treatment >150 mmHg, and/or diastolic pressure >100 mmHg.
3. the American New York Heart Association (New York Heart Association, NYHA)classification of grade 3 or more congestive Heart failure;
4. Arrhythmias of clinical significance, including but not limited to complete leftbundle branch conduction anomaly, degree II atrioventricular block;
5. within 6 months prior to screening of a history of heart attack or a strokewithin three months.

• 8. Active bacterial, fungal or viral infections of clinical significance, includinghepatitis B (hepatitis B virus surface antigen-positive with HBV DNA exceeding 1000IU/ml or meet the criteria for active hepatitis B infection) or hepatitis C (HCV RNApositive), human immunodeficiency virus infection (HIV positive);
• 9. Suffered from a malignant tumor other than the selected indications in the past 5years (other than fully treated cervical carcinoma in situ, non-melanoma basal cell orsquamous epithelial cell skin cancer, local prostate cancer after radical operation,ductal carcinoma in situ after radical operation);
• 10. Women who are pregnant or breastfeeding. Any patient who becomes pregnant duringthe trial should withdraw from the study;
• 11.Rule out any situation that is not suitable for entry into the group. For example,it may cause confusion in research results, interfere with patients' participation inresearch procedures, or have a history of other diseases, treatments, or laboratoryabnormalities, or current evidence that does not meet the clinical benefits ofparticipating in the research. (Such as uncontrollable diabetes, active oruncontrollable infection, etc.).