Benmelstobart-Anlotinib-Chemo for Neoadjuvant Oral Cancer

Inclusion criteria

• Potential subjects must meet all of the following criteria to be eligible for inclusion in this study:
• Age 18-75 years;
• ECOG PS score of 0-1;
• Pathologically confirmed untreated oral squamous cell carcinoma patients, classified as stage III-IVb according to the AJCC (8th edition) staging system;
• Women of childbearing potential must have taken reliable contraceptive measures or have a negative pregnancy test (serum or urine) within 7 days prior to enrollment, and be willing to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterilized. For men, they must agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterilized;

Signed informed consent form by the participant, with good compliance.

Exclusion criteria

Potential subjects must be excluded from the study if they meet any of the following criteria:

• Prior treatment with PD-1/PD-L1/CTLA-4 antibodies.
• Tumor invasion of major blood vessels.
• Requirement for systemic corticosteroid therapy (>10 mg prednisone equivalent per day) or other immunosuppressive treatment within 14 days before administration or during treatment. Inhaled or topical steroids and adrenal corticosteroid replacement therapy at ≤10 mg/day prednisone equivalent are allowed in the absence of active autoimmune disease.
• History of any active immune-related or autoimmune disease, or a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active or uncontrolled severe infection (≥ Grade 2 NCI CTCAE v5.0 infection) within 4 weeks prior to enrollment.
• Coagulation disorders (INR >1.5, prothrombin time (PT) > ULN + 4 sec, or APTT >1.5 × ULN), a tendency for bleeding, or undergoing thrombolytic or anticoagulant therapy. Note: The use of low-dose heparin (adult daily dose of 6,000-12,000 U) or low-dose aspirin (daily dose ≤100 mg) for prophylactic purposes is allowed if INR ≤1.5.
• Imaging evidence of tumor invasion of major blood vessels or tumors highly likely to invade major blood vessels and cause fatal hemorrhage during the study, as assessed by the investigator.
• Any signs or history of a bleeding tendency, regardless of severity. Patients with bleeding or hemorrhagic events (≥CTCAE Grade 2) within 4 weeks prior to randomization, or those with unhealed wounds, ulcers, or fractures.
• Major organ dysfunction:

Hematological abnormalities (without correction via blood transfusion, blood products, G-CSF, or other hematopoietic stimulants within 14 days):

• Hemoglobin (HB) <90 g/L.
• Absolute neutrophil count (ANC) <1.5 × 10⁹/L.
• Platelets (PLT) <100 × 10⁹/L.

Biochemical abnormalities:

• Total bilirubin (TBIL) >1.5 × ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 × ULN.
• Serum creatinine (Cr) >1.5 × ULN or creatinine clearance rate (CCr) <60 mL/min. Doppler ultrasound abnormalities: Left ventricular ejection fraction (LVEF) <60%.

Thyroid function abnormalities: TSH > ULN with abnormal T3 and T4 levels. Renal dysfunction: Urine protein ≥++ on urinalysis or confirmed 24-hour urine protein level ≥1.0 g.

• History of myocardial ischemia (≥Grade I), myocardial infarction, arrhythmia (QTc ≥480 ms), or ≥Grade 2 congestive heart failure (NYHA classification) within 6 months before enrollment.
• Diagnosis of another malignancy within 3 years prior to enrollment.
• Any severe and/or uncontrolled disease, including:

• Poorly controlled hypertension (systolic BP ≥150 mmHg or diastolic BP ≥100 mmHg), history of myocardial ischemia (≥Grade I), myocardial infarction, arrhythmia (QT interval ≥430 ms), or heart failure (NYHA Grade I).
• Active or uncontrolled severe infection.
• Liver cirrhosis, decompensated liver disease, or active hepatitis (HBV or HCV).
• Poorly controlled diabetes (fasting blood glucose (FBG) >10 mmol/L).
• Urine protein ≥2+ and confirmed 24-hour urine protein >1.0 g.
• Presence of long-term unhealed wounds or fractures.
• Lung hemorrhage (>Grade 1 NCI CTC AE v4.0) within 4 weeks before enrollment or hemorrhage in other areas (>Grade 2 NCI CTC AE v4.0) within 4 weeks before enrollment. Patients with a tendency to bleed (e.g., active gastrointestinal ulcers) or those receiving thrombolytic or anticoagulant therapy (e.g., warfarin, heparin, or similar agents).
• History of gastrointestinal perforation and/or fistula within 6 months before treatment initiation; or history of arterial/venous thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism.
• Imaging evidence of tumor invasion of major blood vessels or tumors highly likely to invade major blood vessels and cause fatal hemorrhage, as assessed by the investigator.
• Clinically significant ascites, including any detectable ascites on physical examination or ascites requiring treatment. Patients with only mild asymptomatic ascites detected by imaging may be enrolled.
• Uncontrolled metabolic disorders or other non-malignant systemic diseases or conditions secondary to cancer that may pose a high medical risk and/or create uncertainty in survival assessment.
• Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment.
• History of substance abuse that cannot be discontinued or the presence of psychiatric disorders.
• Any other conditions determined by the investigator that may pose serious risks to patient safety, confound study results, or affect the patient's ability to complete the study.