1. Under pregnancy or lactation, or positive based on blood pregnancy test.

2. Severe allergic to related ingredients in the clinical trial.

3. Received any other investigational treatment within 4 weeks before the first administration or enrolled in another clinical trial the same time (exception: the other treatment is observational and non-investigational or the patient is under follow-up period)

4. Primary central nerve system (CNS) cancer, or subjects with CNS metastasis after localized treatment (except patients without CNS metastasis, clinically stable and neither steroid treatment nor treatment for CNS metastasis).

5. Patients with active autoimmune disease or require systemic steroid treatment. (except patients with cutaneous condition but without systemic treatment, or subjects with asthma in childhood but without intervention after grown-up, or subjects with hypothyroidism mediated by autoimmune dysfunction and receiving thyroxine as replaced treatment)

6. Immunodeficiency including HIV positive, harvested or natural immunodeficiency.

7. Patients with ≥ grade 3 thromboembolic events within 2 years or under thrombolysis treatment.

8. Patients with hereditary or acquired hemorrhagic disease

9. Patients with cardiovascular disease or symptoms:

congestive heart failure (NYHA > 2); history of unstable angina pectoris; miocardial infarction within 48 weeks; clinically significant malignant arrhythmia (except atrial fibrillation and paroxysmal supraventricular tachycardia); Clinically significant prolonged QTcF (Male QTcF > 450 msec, Female QTcF > 470 msec); Uncontrolled hypertension.