Overview
A prospective, randomized, open-label, multicenter Phase 2 trial designed to compare the efficacy and safety of Tislelizumab combined with chemotherapy followed by surgery versus up-front surgery in resectable clinically node-negative head and neck squamous cell carcinoma.
Eligibility
Inclusion Criteria:
Have a histologically confirmed diagnosis of HNSCC which is planned for treatment with
curative intent including surgical resection: stage III/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 days prior
to registration:
Adequate hepatic and renal function as demonstrated by
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 AST/ALT ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert
Syndrome, who can have total bilirubin < 3.0 mg/dL)
Adequate bone marrow function as demonstrated by:
Absolute Neutrophil Count >1,500/µL Platelets > 100 X 103/µL 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 ).