Benmelstobart-Anlotinib-Chemo for Neoadjuvant Oral Cancer

Inclusion Criteria:

• Potential subjects must meet all of the following criteria to be eligible forinclusion in this study:

• Age 18-75 years;

• ECOG PS score of 0-1;

• Pathologically confirmed untreated oral squamous cell carcinoma patients, classifiedas stage III-IVb according to the AJCC (8th edition) staging system;

• Women of childbearing potential must have taken reliable contraceptive measures orhave 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 8weeks 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 8weeks 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 perday) or other immunosuppressive treatment within 14 days before administration orduring treatment. Inhaled or topical steroids and adrenal corticosteroid replacementtherapy at ≤10 mg/day prednisone equivalent are allowed in the absence of activeautoimmune disease.

• History of any active immune-related or autoimmune disease, or a known history ofallogeneic organ transplantation or allogeneic hematopoietic stem celltransplantation.

• 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-doseaspirin (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 toinvade major blood vessels and cause fatal hemorrhage during the study, as assessedby the investigator.

• Any signs or history of a bleeding tendency, regardless of severity. Patients withbleeding or hemorrhagic events (≥CTCAE Grade 2) within 4 weeks prior torandomization, 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):

1. Hemoglobin (HB) <90 g/L.

2. Absolute neutrophil count (ANC) <1.5 × 10⁹/L.

3. Platelets (PLT) <100 × 10⁹/L.

Biochemical abnormalities:

1. Total bilirubin (TBIL) >1.5 × ULN.

2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 × ULN.

3. 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 monthsbefore enrollment.

• Diagnosis of another malignancy within 3 years prior to enrollment.

• Any severe and/or uncontrolled disease, including:

1. Poorly controlled hypertension (systolic BP ≥150 mmHg or diastolic BP ≥100mmHg), history of myocardial ischemia (≥Grade I), myocardial infarction,arrhythmia (QT interval ≥430 ms), or heart failure (NYHA Grade I).

2. Active or uncontrolled severe infection.

3. Liver cirrhosis, decompensated liver disease, or active hepatitis (HBV or HCV).

4. Poorly controlled diabetes (fasting blood glucose (FBG) >10 mmol/L).

5. 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 orhemorrhage in other areas (>Grade 2 NCI CTC AE v4.0) within 4 weeks beforeenrollment. 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 beforetreatment initiation; or history of arterial/venous thrombotic events, such ascerebrovascular accidents (including transient ischemic attacks), deep veinthrombosis, or pulmonary embolism.

• Imaging evidence of tumor invasion of major blood vessels or tumors highly likely toinvade major blood vessels and cause fatal hemorrhage, as assessed by theinvestigator.

• Clinically significant ascites, including any detectable ascites on physicalexamination or ascites requiring treatment. Patients with only mild asymptomaticascites detected by imaging may be enrolled.

• Uncontrolled metabolic disorders or other non-malignant systemic diseases orconditions secondary to cancer that may pose a high medical risk and/or createuncertainty in survival assessment.

• Participation in other anti-tumor clinical trials within 4 weeks prior toenrollment.

• History of substance abuse that cannot be discontinued or the presence ofpsychiatric disorders.

• Any other conditions determined by the investigator that may pose serious risks topatient safety, confound study results, or affect the patient's ability to completethe study.