A Study of SI-B001+SI-B003± Chemotherapy in Patients With Locally Advanced or Metastatic Head and Neck Squamous Cell Carcinoma

A Phase Ib/II Clinical Study of SI-B001+SI-B003 Dual-drug No-combination or Combined Chemotherapy in Patients With Locally Advanced or Metastatic Head and Neck Squamous Cell Carcinoma

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.

Phase Ib: To observe the safety and tolerability of SI-B001+SI-B003 combination and to determine the recommended dose (RP2D) for Phase II clinical studies in locally advanced or metastatic head and neck squamous cell carcinoma indications. To evaluate the initial efficacy, pharmacokinetic characteristics and immunogenicity of SI-B001+SI-B003 in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Phase II: To evaluate the efficacy of SI-B001+SI-B003 dual-agent chemotherapy in patients with locally advanced or metastatic head and neck squamous cell carcinoma. The safety, tolerability, PK/PD and immunogenicity of SI-B001+SI-B003 combined chemotherapy in patients with locally advanced or metastatic head and neck squamous cell carcinoma were evaluated.

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.