Overview

Phase Ib: To observe the safety and tolerability of SI-B001+SI-B003 in combination and to identify RP2D in locally advanced or metastatic head and neck squamous cell carcinoma indications. Initial efficacy, pharmacokinetic characteristics and immunogenicity were evaluated. Phase II: To evaluate the efficacy of SI-B001+SI-B003 two-drug combination chemotherapy. Safety and tolerance, PK/PD, immunogenicity were evaluated.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Histologically or cytologically confirmed head and neck squamous cell carcinoma occurring only in the oral cavity, oropharynx, hypopharynx, and larynx;
6. Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. Performance status score: ECOG ≤1;
9. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
11. Organ function levels must meet the requirements;
12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
13. Urine protein ≤1+ or ≤1000 mg/24h;
14. Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 24 weeks after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.

Exclusion Criteria:

1. Squamous cell carcinoma originating from the nasopharynx, salivary glands, nasal sinuses, skin, or with an unknown primary site;
2. For Phase II patients, either: a) those suitable for and willing to undergo local therapy; or b) those who have received systemic chemotherapy, excluding chemotherapy administered as part of multimodal treatment for locally advanced disease;
3. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (leptomeningeal metastases) and/or spinal cord compression;
4. Participation in any other clinical trial within 4 weeks prior to the administration of this trial's investigational product (based on the last dose date);
5. Receipt of chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, or other antitumor treatments within 4 weeks before the first dose of the study drug;
6. Major surgery (as defined by the investigator) within 4 weeks prior to the first dose;
7. Requirement for systemic corticosteroids or immunosuppressive therapy within 2 weeks before the study drug administration;
8. Pulmonary diseases graded as ≥Grade 3 according to NCI-CTCAE v5.0; current or history of interstitial lung disease (ILD);
9. Active infection requiring intravenous anti-infective therapy;
10. Prior immunotherapy leading to ≥Grade 3 immune-related adverse events (irAE) or ≥Grade 2 immune-related myocarditis;
11. Use of live attenuated vaccines within 4 weeks before the first dose of the study drug;
12. Use of immunomodulatory drugs (including but not limited to thymosin, interleukin-2, interferon, etc.) within 14 days before the first dose of the study drug;
13. Patients at risk of active autoimmune diseases or with a history of autoimmune diseases;
14. History of other malignancies within 5 years before the first dose;
15. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
16. Poorly controlled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg);
17. History of severe cardiovascular or cerebrovascular diseases;
18. Previous allogeneic stem cell, bone marrow, or organ transplantation;
19. Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
20. History of hypersensitivity to recombinant humanized antibodies or any excipients of SI-B001 or SI-B003;
21. History of severe infusion reactions (CTCAE Grade ≥3) to antibody therapy;
22. History of autologous or allogeneic stem cell transplantation;
23. Pregnant or lactating women;
24. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.