A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SI-B036 Bispecific Antibody Injection in Patients With Locally Advanced or Metastatic Head and Neck Tumors and Other Solid Tumors
This is an open-label, multicenter, non-randomized Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SI-B036 Bispecific Antibody Injection in patients with locally advanced or metastatic head and neck tumors and other solid tumors.
The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion cohort phase (Phase Ib).
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.
[{"measure":"Phase Ia: Dose limiting toxicity (DLT)","timeFrame":"Up to 21 days after the first dose"},{"measure":"Phase Ia: Maximum tolerated dose (MTD)","timeFrame":"Up to 21 days after the first dose"},{"measure":"Phase Ib: Recommended Phase II Dose (RP2D)","timeFrame":"Up to approximately 24 months"}]