A Study of SI-B001, an EGFR/HER3 Bispecific Antibody, in Locally Advanced or Metastatic Epithelial Tumors

Exclusion Criteria

• •1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration.
• •2. If there is a history of vaccination within 3 months prior to the first administration, it is allowed to receive inactivated influenza vaccine within 30 days prior to the first administration, and the treatment of live attenuated vaccine is not allowed.
• •3. Participants with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc.
• •4. Participants with prolonged QT interval (male QTc\> 450 msec or female QTc\> 470 msec), complete left bundle branch block, III grade atrioventricular block.
• •5. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
• •6. Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection.
• •7. Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg).
• •8. Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, including participants with resting dyspnea, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD).
• •9. Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis or stable epidural spinal cord compression history can be included. Stable is defined as: a. With or without antiepileptic drugs, the seizure-free state lasts for more than 12 weeks; b. There is no need to use glucocorticoids; c. Continuous multiple MRI (scanning interval at least 8 weeks) showed a stable state in imaging.
• •10. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of SI-B001.
• •11. Participants have a history of autologous or allogeneic stem cell transplantation.
• •12. In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is\> 360 mg/m2.
• •13. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number\> 104) or hepatitis C virus (HCV) infection.
• •14. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
• •15. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.
• •16. Participated in another clinical trial within 4 weeks prior to participating in the study.