Previous studies confirmed locally advanced oral/oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 monoclonal antibody Tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy or chemoradiotherapy plus Tislelizumab in LA OSCC or OPSCC.

Inclusion Criteria:

• Cytological or histological diagnosis of initially or potentially surgically resectable Local advanced oral/oropharyngeal squamous cell carcinoma (stage III-IV).
• Plan to proceed neoadjuvant therapy.
• No prior anti-cancer treatment (include surgery, radiotherapy and systemic therapy) for oral/oropharyngeal squamous cell carcinoma.
• Clinically evaluable lesions per RECIST1.1.
• The age of signing the informed consent is 18-80 years old, regardless of gender.
• ECOG performance score 0-1.
• Estimated survival time≥6 months (this criterion overlaps with other inclusion criteria and must meet the following: ECOG score 0-1; Vital organ function meets the inclusion criteria in Article 8; Oral or oropharyngeal cancer does not involve the internal carotid artery; No subcutaneous metastases; No distant metastasis).
• Adequate organ function as follows: 1) Leukocyte count ≥ 3,000/mm3; 2) Absolute neutrophil count ≥ 1,500/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum creatinine ≤ 1.5 × ULN OR CrCl≥50 ml/min（Cockcroft-Gault）; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN;
• Subjects able and willing to follow research and follow-up procedures.
• For male and female subjects of childbearing age must agree to use adequate contraception throughout the study period and for 6 months after the end of treatment.
• Subjects voluntarily joined the clinical study and signed the informed consent.

Exclusion Criteria:

• Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways.
• History of allergy, and may have a potential allergy or intolerance to the investigational drug and its similar biologics.
• Participated in clinical trials of other antitumor drugs within 4 weeks prior to initial administration; Or receive live attenuated vaccine within 4 weeks prior to initial administration or during the study period;
• Subjects with concurrent other active malignancies. History of other types for cancer within past 5 years (exclude adequately treated skin squamous cell carcinoma or controlled skin basal cell carcinoma).
• Advanced subjects with symptoms, visceral dissemination, and a short-term risk of life-threatening complications (including uncontrolled massive exudation [pleural, pericardial, peritoneal], pulmonary lymphangitis, and more than 30% liver involvement).
• Subjects with active autoimmune disease or history of refractory autoimmune disease.
• Subjects with grade II or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms in men and ≥470 ms in women), NYHA class III-IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) <50% on echocardiography, myocardial infarction within 6 months before enrollment, New York Heart Association class II or higher heart failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or electrocardiogram suggestive of acute ischemia or active conduction system abnormalities;
• Severe infection (e.g. requiring intravenous antibiotics, antifungal or antiviral medication) within 4 weeks before first dose, or unexplained fever >38.5°C during screening/before first dose;
• Subjects with a history of abuse of psychotropic substances and unable to withdraw from them or with mental disorders;
• Subjects undergone major surgery or have an open wound or fracture within 4 weeks before the first dose;
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the analytical method) or co-infection of hepatitis B and hepatitis C;
• Central nervous system metastasis;
• Subjects with a history of genetic or acquired bleeding or coagulation dysfunction (eligibility criteria at the investigator's discretion);
• Other conditions that the investigator determined were inappropriate for participation in the study.