Neoadjuvant Sintilimab in Combination With Carboplatin and Nab-paclitaxel in Resectable Oral Cavity or Oropharyngeal Squamous Cell Carcinoma

Inclusion Criteria:

• Have a histologically confirmed diagnosis of OSCC or OPSCC which is planned fortreatment with curative intent including surgical resection：stage II-IVA.

• Greater than or equal to 18 and less than 80 years of age at time of study entry.

• ECOG performance status of 0 or 1.

• Measurable disease as per RECIST 1.1.

• Patients must have no prior exposure to immune-mediated therapy, including anti-cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1,anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines.

• Screening labs must meet the following criteria and must be obtained within 14 daysprior to registration:

1. Adequate hepatic and renal function as demonstrated by
2. Serum creatinine < 1.5 X ULN or CrCl > 40mL/min (if using theCockcroft-Gault formula below):

• Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 xserum creatinine (mg/dL)）
• Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 xserum creatinine (mg/dL))x 0.85

2. AST/ALT ≤ 3 x ULN

3. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, whocan have total bilirubin < 3.0 mg/dL)

4. Adequate bone marrow function as demonstrated by:

5. Absolute Neutrophil Count >1,500/µL

6. Platelets > 100 X 103/µL

7. Hemoglobin > 9.0 g/dL

• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 21 days of study enrollment.

• Women of reproductive potential must use highly effective contraception methods toavoid pregnancy for 23 weeks after the last dose of study drugs; "women ofreproductive potential" is defined as any female who has experienced menarche andwho has not undergone surgical sterilization (hysterectomy or bilateraloophorectomy) or who is not postmenopausal; menopause is defined clinically as 12months of amenorrhea in a woman over 45 in the absence of other biological orphysiological causes; in addition, women under the age of 55 must have a documentedserum follicle stimulating hormone (FSH) level less than 40 mIU/mL.

• Men of reproductive potential who are sexually active with women of reproductivepotential must use any contraceptive method with a failure rate of less than 1% peryear; men who are receiving the study medications will be instructed to adhere tocontraception for 31 weeks after the last dose of study drugs; men who areazoospermic do not require contraception.

• Ability to understand and willingness to sign an IRB approved written informedconsent document (or that of legally authorized representative, if applicable).

• Subject is willing and able to comply with the protocol for the duration of thestudy including undergoing treatment and scheduled visits and examinations includingfollow up.

• Subjects must agree to allow use of any pre-treatment tissue remaining afterdefinitive diagnosis is made (ie, archival and or fresh tissue) for researchpurposes. In addition, subjects must consent to allow use of their residualpost-operative tissue for research purposes.

Exclusion Criteria:

• Is currently participating in or has participated in a study of an investigationalagent within 4 weeks of the first dose of treatment or has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4weeks earlier.

• Has had another known invasive malignancy within the previous 5 years and/or has hadsurgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5years for a known malignancy prior to study day 0.

• If subject received major surgery for any other reason, they must have recoveredadequately from the toxicity and/or complications from the intervention prior tostarting therapy.

• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -5. Inhaled or topical steroids, and adrenal replacement steroid > 10mg daily prednisone equivalent, are permitted in the absence of active autoimmunedisease.

• Has an active autoimmune disease requiring systemic steroid treatment within thepast 3 months or a documented history of clinically severe autoimmune disease, or asyndrome that requires systemic steroids.

• Active, known or suspected autoimmune disease. Note: Subjects are permitted toenroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism dueto autoimmune condition only requiring hormone replacement, psoriasis not requiringsystemic treatment, or conditions not expected to recur in the absence of anexternal trigger .

• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

• Has an active infection requiring systemic therapy.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4antibody, or any other antibody or drug specifically targeting T-cell costimulationor immune checkpoint pathways.

• A history of allergic reaction attributed to compounds of similar chemical orbiologic composition to the treatment or other agents used in the study.

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thesubject's participation for the full duration of the trial, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visitthrough 23 weeks after the last dose of trial treatment.

• Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2antibodies).

• Has known active Hepatitis B or C.

• Known history of active TB ( bacillus tuberculosis ).