Neoadjuvant Toripalimab or Toripalimab in Combination With Carboplatin and Nab-paclitaxel in Untreated HNSCC (HNSCC-002)
Neoadjuvant Toripalimab or Toripalimab in Combination With Carboplatin and Nab-paclitaxel in Untreated HNSCC (HNSCC-002)
This proposed study will evaluate the efficacy and safety of preoperative administration of
 Toripalimab or Toripalimab combined with nab-paclitaxel and carboplatin in Head and Neck
 Squamous Cell Carcinoma (HNSCC) who are about to undergo surgery，and it will be helpful for
 comprehensive exploratory characterization of tumor immune microenvironment and circulating
 immune cells in these patients. Data obtained in this trial will provide valuable information
 for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in
 HNSCC. We are also eager to identify potential biomarkers of response and toxicity that will
 enable patients with HNSCC who are most likely to benefit to receive anti-PD-1 therapy and,
 to the contrary, reduce the risk of toxicity and ineffective therapy in patients who are less
 likely to benefit from it.
Inclusion Criteria:

 -  Have a histologically confirmed diagnosis of HNSCC which is planned for treatment with
 curative intent including surgical resection.

 -  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 , anti-programmed cell death 1, anti-programmed cell
 death 1 ligand 1 , 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 days
 prior to registration:

 1. Adequate hepatic and renal function as demonstrated by

 1. Serum creatinine < 1.5 X ULN or CrCl > 40mL/min (if using the
 Cockcroft-Gault formula below):

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

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

 2. AST/ALT ≤ 3 x ULN

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

 2. Adequate bone marrow function as demonstrated by:

 1. Absolute Neutrophil Count >1,500/µL

 2. Platelets > 100 X 103/µL

 3. 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 to
 avoid pregnancy for 23 weeks after the last dose of study drugs; "women of
 reproductive potential" is defined as any female who has experienced menarche and who
 has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or
 who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea
 in a woman over 45 in the absence of other biological or physiological causes; in
 addition, women under the age of 55 must have a documented serum follicle stimulating
 hormone (FSH) level less than 40 mIU/mL.

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

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

 -  Subject is willing and able to comply with the protocol for the duration of the study
 including undergoing treatment and scheduled visits and examinations including follow
 up.

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

 Exclusion Criteria:

 -  Is currently participating in or has participated in a study of an investigational
 agent 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 4
 weeks earlier.

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

 -  If subject received major surgery for any other reason, they must have recovered
 adequately from the toxicity and/or complications from the intervention prior to
 starting 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 > 10 mg
 daily prednisone equivalent, are permitted in the absence of active autoimmune
 disease.

 -  Has an active autoimmune disease requiring systemic steroid treatment within the past
 3 months or a documented history of clinically severe autoimmune disease, or a
 syndrome that requires systemic steroids.

 -  Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll
 if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to
 autoimmune condition only requiring hormone replacement, psoriasis not requiring
 systemic treatment, or conditions not expected to recur in the absence of an external
 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-4
 antibody, or any other antibody or drug specifically targeting T-cell costimulation or
 immune checkpoint pathways.

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

 -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
 that might confound the results of the trial, interfere with the subject's
 participation for the full duration of the trial, or is not in the best interest of
 the subject to participate, in the opinion of the treating investigator.

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

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

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

 -  Has known active Hepatitis B or C.

 -  Known history of active TB ( bacillus tuberculosis ).