SI-B036 in head and neck and other solid tumors: a first-in-human study

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements;
2. No gender restriction;
3. Age: ≥18 years and ≤75 years;
4. Life expectancy ≥3 months;
5. Locally advanced or metastatic head and neck tumors and other solid tumors;
6. Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary or metastatic lesions within 2 years;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. ECOG performance status score of 0 or 1;
9. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
10. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
11. Organ function levels must meet the protocol requirements;
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN);
13. Urine protein ≤2+ or ≤1000 mg/24h;
14. For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days prior to the start of treatment, with a negative result, and they must not be lactating. All enrolled patients (regardless of gender) must adopt adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after the completion of treatment;
15. Participants must be capable of and willing to comply with the study visits, treatment plans, laboratory tests, and other study-related procedures as specified in the protocol.

Exclusion Criteria:

1. Received chemotherapy, biotherapy, immunotherapy, or other systemic anti-tumor therapies within 4 weeks or 5 half-lives prior to the first dose;
2. Received immunosuppressive medications within 2 weeks prior to the first dose;
3. History of severe cardiac or cerebrovascular disease;
4. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
5. Active autoimmune diseases and inflammatory diseases;
6. History of ≥ Grade 3 toxicity related to anti-angiogenic therapy when previously receiving such treatment;
7. Diagnosis of another solid malignancy within 5 years prior to the first dose;
8. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
9. Uncontrolled hypertension;
10. Diabetes mellitus with poor glycemic control;
11. History of interstitial lung disease (ILD) requiring corticosteroid therapy, or current ILD, or ≥ Grade 2 radiation pneumonitis;
12. Concurrent pulmonary disease resulting in severe impairment of respiratory function;
13. Active central nervous system (CNS) metastases;
14. History of allergy to recombinant humanized or human-mouse chimeric antibodies, or allergy to any excipient of SI-B036;
15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
16. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
17. Active infection requiring systemic therapy within 4 weeks prior to the first dose of study drug;
18. Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first dose of study drug;
19. Imaging findings indicate that the tumor has invaded or encased the great thoracic vessels, pericardium, or heart;
20. Clinically significant hemorrhage or obvious bleeding tendency within 4 weeks prior to screening;
21. History of fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first dose;
22. Use of another investigational drug within 4 weeks or 5 half-lives prior to the first dose;
23. Pregnant or lactating women;
24. Any other conditions that, in the investigator's judgment, make the participant unsuitable for enrollment in this clinical trial.