Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer

Exclusion Criteria

• •1. Other histological subtypes of thyroid cancers excluding DTC (such as Anaplastic Thyroid Carcinoma and Medullary Thyroid Carcinoma).
• •2. Known hypersensitivity to any component of ST-1898 tablets.
• •3. Participants who have received any antitumor treatment within 4 weeks or 5 half-lives of the agent (contingent on the shorter time) prior to the first dose of study drug.
• •4. Patients who underwent major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of study drug.
• •5. Serious non-healing wound/ulcer/bone fracture.
• •6. ≥ grade 3 bleeding episodes within 6 months prior to first dose of study treatment, or currently ≥ grade 2 hemorrhage, with high bleeding risks (such as coagulation disorders, tracheobronchial infiltration with significant bleeding, active gastrointestinal ulcer and esophageal varices)
• •7. Active hemoptysis or more than 0.5 teaspoon (2.5 mL) of hemoptysis per day within 2 months before first dose of study treatment
• •8. Subjects with antiplatelet agents treatment (low-dose aspirin ≤100 mg/day is permitted).
• •9. Current or previous severe retinopathy who, in the judgment of the Investigator or specialist, are not suitable for enrollment
• •10. Significant cardiovascular impairment, including but not limited to:
• •1. Serious arrhythmia or cardiac conduct abnormality, such as degree II-III atrioventricular block or ventricular arrhythmia needs to be treated.
• •2. QTcF interval extension (by the Fridericia formula): male \>450 ms, female \>480 ms
• •3. Acute coronary syndrome, stroke, deep vein thrombosis, pulmonary- thromboembolism, arterial thrombosis, congestive heart failure, aortic dissection etc.
• •4. New York Heart Association Class ≥ II
• •5. Uncontrolled hypertension, as defined by a sustained blood pressure (BP) \> 140/90 mmHg.
• •11. Known brain metastasis unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and with a stable dose of corticosteroid treatment before first dose of study treatment.
• •12. Interstitial lung disease or radiation pneumonia in need of glucocorticoids intervention
• •13. Subjects with malignant tumors in the last 5 years (not including non-melanoma skin cancer, breast cancer or cervical cancer in situ, and Non-Muscle-invasive bladder cancer have been cured)
• •14. Receiving chronic concomitant treatment of strong CYP3A4 inducers, CYP3A4 inhibitors or CYP3A4 substrate with a narrow therapeutic window within 2 weeks prior to study drug administration,
• •15. Prior treatment of BRAF inhibitors.
• •16. Has not recovered from toxicities caused by prior therapy to CTCAE ≤Grade 1 (except for ≤Grade 2 peripheral neuropathy, alopecia, and other events judged tolerable by the Investigator and without safety risks).
• •17. HIV antibodies or Treponema pallidum antibodies positive, active hepatitis B (HBV-DNA≤ 2×ULN allowed to enroll), hepatitis C virus (HCV) antibody-positive and HCV-RNA- positive, or other active hepatitis, clinically significant moderate-to-severe cirrhosis. Prophylactic antiviral therapy other than interferon are allowed.
• •18. Acute bacterial, viral or fungal infections (any infection requiring systemic treatment)
• •19. Females who are pregnant or breastfeeding.
• •20. Drug or alcohol dependents.
• •21. Significant disorder of neurology or mental disease or poorly compliance.
• •22. Subjects with oral administration impossible, or in the conditions of malabsorption as determined by the investigator, such as dysphagia and intestinal obstruction, etc..
• •23. Uncontrolled pleural effusion, pericardial effusion, abdominal effusion requiring frequent drainage or medical intervention (clinically significant recurrence requiring additional intervention within 2 weeks after intervention, excluding exudate cytology) before first dose of study treatment.
• •24. Any history of other serious systemic diseases, or any other reason that might interfere with participation in trial or interfere with interpretation of trial results, in the judgement of the Investigator, that are not qualified to participate in this trial.