Sintilimab Plus Chemotherapy as Neoadjuvant and Adjuvant Treatment for Locally Advanced Oral Squamous Cell Carcinoma

Prior treatment

• Prior treatment targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other therapies targeting T-cell costimulatory or immune checkpoint pathways.
• Participation in another interventional clinical trial or use of an investigational drug or device within 4 weeks prior to the first dose.
• Use of traditional Chinese medicines or immunomodulatory agents with OSCC indications (e.g., thymosin, interferon, interleukin) within 2 weeks before first dosing; local therapy for pleural effusion control is permitted.
• 1\. Hypothyroidism controlled with thyroid hormone replacement therapy.
• 3\. Adrenal or pituitary insufficiency treated with physiologic doses of corticosteroids.
• 1\. Systemic corticosteroid therapy within 1 week prior to the first dose is prohibited.
• 2\. Use of other immunosuppressive drugs is prohibited.
• 3\. Intranasal, inhaled, or topical corticosteroids are permitted.
• 4\. Physiologic doses of corticosteroids (e.g., prednisone ≤10 mg/day or equivalent) are permitted.
• Prior systemic antitumor therapy, except patients who have had ≥12 months of treatment-free interval between the last chemotherapy and initiation of neoadjuvant therapy.
• Previous allogeneic organ or hematopoietic stem cell transplantation (excluding corneal transplantation).
• Failure to recover to baseline or ≤ grade 1 (except fatigue or alopecia) from adverse events or complications of prior interventions before enrollment.
• 1\. HBV viral load \<1000 copies/mL (200 IU/mL) and receiving antiviral therapy during the study to prevent reactivation.
• Receipt of a live vaccine within 30 days prior to the first dose (inactivated vaccines, such as inactivated influenza vaccine, are permitted; intranasal live vaccines are not allowed).
• 2\. Vascular disorders: history of unstable angina, myocardial infarction, transient ischemic attack, or stroke within 6 months before enrollment.
• 4\. Pulmonary disorders: noninfectious pneumonitis requiring corticosteroid therapy within 1 year prior to the first dose, or active interstitial lung disease.

Other illness

• History of radiotherapy involving the head, neck, or maxillofacial regions.
• History of active autoimmune disease within the past 2 years requiring systemic therapy (e.g., corticosteroids or immunosuppressants). Exceptions include:
• 2\. Diabetes mellitus controlled with insulin.
• Known hypersensitivity to sintilimab, carboplatin, cisplatin, nab-paclitaxel, or any of their excipients.
• Known human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive).
• 2\. Subjects who are anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV-DNA(-) do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation.
• Active hepatitis C infection (HCV antibody positive with HCV-RNA above the lower limit of detection).
• Presence of severe or uncontrolled systemic diseases, including but not limited to:
• 1\. Cardiac disorders: severe arrhythmias (e.g., complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmia, or persistent atrial fibrillation), unstable angina, or congestive heart failure (NYHA class ≥ II).
• 3\. Poorly controlled hypertension (systolic BP \>140 mmHg or diastolic BP \>90 mmHg).
• 5\. Infectious diseases: active infections requiring systemic treatment, or severe uncontrolled infections.
• 6\. Active pulmonary tuberculosis.
• 7\. Gastrointestinal disorders: clinically active diverticulitis, intra-abdominal abscess, or intestinal obstruction.
• 8\. Hepatic disorders: liver cirrhosis, decompensated liver disease, or acute/chronic active hepatitis.
• 11\. Psychiatric disorders: severe mental illness that may affect treatment compliance.
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.

Lab values

• Untreated active hepatitis B infection (HBsAg positive with HBV-DNA above the ULN). Subjects meeting the following criteria may be enrolled:
• 9\. Poorly controlled diabetes mellitus: fasting blood glucose (FBG) \>10 mmol/L.

Other

• Use of immunosuppressive agents:
• Pregnant or breastfeeding women.
• 10\. Renal dysfunction: urine protein ≥++ on urinalysis and 24-hour urinary protein \>1.0 g.

• Aged 18 to 75 years at the time of enrollment.
• ECOG Performance Status (PS) score of 0-1.
• Primary lesion pathologically confirmed as oral squamous cell carcinoma (OSCC), including tumors of the anterior two-thirds of the tongue, gingiva, buccal mucosa, floor of the mouth, hard palate, or retromolar trigone.
• Clinical stage III or IVA, defined as T1-2 with N1-2, or T3-4a and/or N0-2, according to the AJCC 8th edition OSCC TNM staging system.
• Willingness to undergo surgical treatment.
• Presence of at least one measurable lesion as defined by RECIST v1.1 criteria.
• Voluntary participation with full understanding and signing of the informed consent form, and willingness to comply with study procedures.
• Adequate major organ function, meeting all of the following laboratory criteria:
• 1\. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without granulocyte colony-stimulating factor (G-CSF) administration within 14 days prior to testing.
• 2\. Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days.
• 3\. Hemoglobin \> 90 g/L without blood transfusion or erythropoietin use within the previous 14 days.
• 4\. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN); ≤ 3 × ULN in cases of Gilbert's syndrome or non-hepatic indirect bilirubin elevation.
• 5\. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ≤ 5 × ULN for patients with hepatic involvement.
• 6\. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min.
• 7\. Adequate coagulation function, defined as INR or prothrombin time (PT) ≤ 1.5 × ULN.
• 8\. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with abnormal TSH may be enrolled if total T3 (or FT3) and FT4 are within normal limits.
• 9\. Normal myocardial enzyme profile (minor laboratory abnormalities deemed clinically insignificant by the investigator are acceptable).
• 10\. For women of childbearing potential, a negative urine or serum pregnancy test within 3 days prior to the first dose of study treatment (Cycle 1, Day 1) is required. If the urine test is indeterminate, a serum test must be performed. Non-childbearing women are defined as those who have been postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy.
• 11\. All participants (male or female) with reproductive potential must agree to use highly effective contraception (annual failure rate \<1%) during the entire treatment period and for at least 120 days after the last study drug dose or 180 days after the last chemotherapy dose.