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

Inclusion Criteria:

1. Participants must sign the informed consent form voluntarily and follow the planrequirements.

2. No gender limit.

3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib).

4. Expected survival time ≥ 3 months.

5. Locally advanced or metastatic epithelial malignancies are confirmed byhistopathology and/or cytology that are incurable or currently without standardtreatment.

6. Participants must agree to provide archived tumor tissue specimens or fresh tissuesamples within 6 months of the primary tumor or metastasis; in phase Ia, if theparticipant is unable to provide tumor tissue samples, the investigator willevaluate whether the participant could be enrolled if other criteria are fit to jointhe group.

7. Participants must have at least one measurable lesion that meets the definition ofRECIST v1.1.

8. Physical fitness score ECOG 0 or 1 point.

9. The toxicity of previous anti-tumor treatments has been restored to NCI-CTCAE v5.0definition ≤ 1 (except for hair loss).

10. No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%, (hypersensitivity) troponin T<ULN.

11. The organ function must meet the following requirements and standards: a) Bonemarrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN),AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULNfor liver metastases; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinineclearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).

12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activatedpartial thromboplastin time (APTT)≤1.5ULN.

13. Urine protein≤2%2B (measured with test paper) or≤1000mg/24h (urine).

14. For premenopausal women with childbearing potential, a pregnancy test must be takenwithin 7 days prior to the start of treatment. Serum or urine pregnancy must benegative and must be non-lactating; all participants (regardless of male or female)in the group should be treated throughout the treatment. Adequate barriercontraceptive measures should be taken during the treatment and 6 months after thetreatment.

Exclusion Criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, majorsurgery, 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 6weeks prior to the first administration; oral fluorouracil-like drugs such as S-1,capecitabine, or palliative radiotherapy within 2weeks prior to the firstadministration.

2. If there is a history of vaccination within 3 months prior to the firstadministration, it is allowed to receive inactivated influenza vaccine within 30days prior to the first administration, and the treatment of live attenuated vaccineis not allowed.

3. Participants with history of severe heart disease, such as: symptomatic congestiveheart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of transmural myocardial infarction, unstable anginapectoris etc.

4. Participants with prolonged QT interval (male QTc> 450 msec or female QTc> 470msec), complete left bundle branch block, III grade atrioventricular block.

5. Active autoimmune diseases and inflammatory diseases, such as: systemic lupuserythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis,inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type Idiabetes, hypothyroidism that can be controlled only by alternative treatment, andskin diseases that do not require systemic treatment (such as vitiligo, psoriasis).

6. Other malignant tumors were diagnosed within 5 years prior to the firstadministration with the following exceptions: basal cell carcinoma of the skin,squamous cell carcinoma of the skin and/or carcinoma in situ after radicalresection.

7. Participants with poorly controlled hypertension by two kinds of antihypertensivedrugs (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 withstable brain metastasis or stable epidural spinal cord compression history can beincluded. Stable is defined as: a. With or without antiepileptic drugs, theseizure-free state lasts for more than 12 weeks; b. There is no need to useglucocorticoids; 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 orhuman-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 ofanthracyclines is> 360 mg/m2.

13. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, activehepatitis B virus infection (HBV-DNA copy number> 104) or hepatitis C virus (HCV)infection.

14. Participants with active infections requiring systemic treatment, such as severepneumonia, bacteremia, sepsis, etc.

15. Other conditions that the investigator believes that it is not suitable forparticipating in this clinical trial.

16. Participated in another clinical trial within 4 weeks prior to participating in thestudy.