A Pilot Trial of Neoadjuvant Sulfate Emactinib Plus Chemo-immunotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck.
The goal of this clinical trial is to evaluate the efficacy and safety of a novel combination therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). The therapy combines the JAK1 inhibitor Sulfamethoxazole, the anti-PD-L1 antibody Adebrelimab, and chemotherapy (Nab-paclitaxel + Cisplatin) as a neoadjuvant treatment (given before surgery). The main questions it aims to answer are: * For patients with resectable locally advanced HNSCC: Can this combination improve the pathological complete response (pCR) rate (the absence of viable cancer cells in the surgical specimen) compared to current neoadjuvant therapies? * For patients with potentially resectable or unresectable locally advanced HNSCC: Can this combination improve the objective response rate (ORR) (the percentage of patients with significant tumor shrinkage), potentially making surgery possible or reducing its scope? Researchers will also assess secondary outcomes including event-free survival (EFS), overall survival (OS), and the safety profile of the combination. Participants will: * Receive neoadjuvant treatment with the combination of Sulfamethoxazole, Adebrelimab, and chemotherapy. A key feature is the timed sequencing of the JAK inhibitor, which will be started on day 8 of each treatment cycle. * Be evaluated for surgery after the neoadjuvant treatment. For those who undergo surgery, the pathological response will be analyzed. * Have regular follow-up assessments, including imaging studies (such as CT or MRI scans) and safety monitoring, to evaluate long-term treatment response, survival, and side effects. * Provide tissue and/or blood samples for exploratory biomarker analysis (e.g., Interferon-Stimulated Gene signature) to help identify patients who benefit most from this treatment.
• ECOG Performance Status of 0-1.
• Histologically and/or cytologically confirmed Stage III-IVA head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx).
• Classified according to the Asia-Pacific multidisciplinary consensus (Y.Guo et al., Oral Oncol 2024):
‣ Cohort A: Resectable\*\* (amenable to upfront surgery): T2N2-3M0, T3-4N0-2M0 (AJCC 8th edition).
⁃ Cohort B: Potentially Resectable:\*\* Cases with relative contraindications to surgery (e.g., cervical lesion directly invading skin, anterior 2/3 tongue tumor extending below the hyoid level, extension to the vallecula) or where surgery would cause significant disfigurement/functional loss, requiring discussion by an MDT (head \& neck surgery, radiology) to weigh risks vs. non-surgical options.
⁃ Cohort C: Unresectable: Tumor extensively invading skull base, extending to nasopharynx/deep nasopharyngeal wall, invading/encasing carotid artery, extending to mediastinal structures, prevertebral fascia, or cervical spine; T3-4 (N0-3) or any N2a-3 (T1-4) M0 (AJCC 8th edition).
• Biomarker: Peripheral blood flow cytometry analysis showing that PD-1+TIM-3+CD8+ exhausted T cells account for \>10% of CD8+ T cells.
• Adequate baseline organ function within 14 days prior to enrollment:
‣ Hematological: White Blood Cell count (WBC) ≥4000/μL, Absolute Neutrophil Count (ANC) ≥2000/μL, Hemoglobin (HGB) ≥9 g/dL, Platelet count (PLT) ≥100,000/μL.
⁃ Renal: Serum creatinine \<1.5 times the Upper Limit of Normal (ULN) OR Creatinine Clearance (CrCl) \>60 mL/min (calculated by Cockcroft-Gault formula).
⁃ Hepatic: Total bilirubin ≤1.5x ULN (except subjects with Gilbert's syndrome, who may have total bilirubin \<3x ULN); Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤3x ULN; Alkaline Phosphatase (ALP) ≤3x ULN; Albumin (ALB) ≥3 g/dL.
• Ability to understand and willingness to sign the Informed Consent Form. Subjects must be willing and able to comply with the protocol, including receiving treatments and scheduled visits/examinations, including follow-up.