Sintilimab Plus Chemotherapy as Neoadjuvant and Adjuvant Treatment for Locally Advanced Oral Squamous Cell Carcinoma: A Multicenter, Open-label, Randomized, Phase III Clinical Study
This is a multicenter, open-label, randomized phase III clinical trial evaluating perioperative treatment with sintilimab combined with chemotherapy in patients with locally advanced oral squamous cell carcinoma. Despite standard treatment with surgery followed by postoperative radiotherapy or chemoradiotherapy, patients with locally advanced oral squamous cell carcinoma remain at high risk of recurrence or metastasis. Recent evidence, including results from the KEYNOTE-689 study, suggests that perioperative immunotherapy may improve survival outcomes, and this approach has been incorporated into NCCN guidelines. Combining immunotherapy with chemotherapy may further improve prognosis in this patient population. Eligible participants will be randomly assigned to either an experimental group or a control group. The experimental group will receive neoadjuvant sintilimab combined with chemotherapy followed by surgery and postoperative treatment based on pathological response. Patients with major pathological response (MPR) will receive adjuvant sintilimab, while patients without MPR will receive postoperative radiotherapy or concurrent chemoradiotherapy combined with sintilimab. The control group will receive standard treatment consisting of surgery followed by postoperative radiotherapy or chemoradiotherapy as clinically indicated. The primary objective of the study is to compare event-free survival between the two groups. Secondary objectives include overall survival, pathological response, safety, and treatment-related adverse events. The results of this study may help optimize perioperative treatment strategies and improve outcomes for patients with locally advanced oral squamous cell carcinoma.
• 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.