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

Eligibility

Criteria

Inclusion Criteria:

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

  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 by
     histopathology and/or cytology that are incurable or currently without standard
     treatment.

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

  7. Participants must have at least one measurable lesion that meets the definition of
     RECIST 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 v5.0
     definition ≤ 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) Bone
     marrow 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 ULN
     for liver metastases; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine
     clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).

 12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated
     partial 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 taken
     within 7 days prior to the start of treatment. Serum or urine pregnancy must be
     negative and must be non-lactating; all participants (regardless of male or female)
     in the group should be treated throughout the treatment. Adequate barrier
     contraceptive measures should be taken during the treatment and 6 months after the
     treatment.

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.

• Gender: all
• Age: 18
• Healthy volunteers: no
• Therapy type: -
• Therapy Specification: -