A Phase 3, Prospective，Multicenter, Randomized Open-Label Trial to Compare the Efficacy and Safety of Tislelizumab (BGB A317, Anti-PD1 Antibody) Combined With Chemotherapy Followed By Surgery Versus Up-Front Surgery as Treatment for Resectable Head And Neck Squamous Cell Carcinoma
Overview
- Phase
- Phase 3
- Intervention
- Tislelizumab（neoadjuvant）
- Conditions
- Head and Neck Squamous Cell Carcinomas
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 537
- Locations
- 3
- Primary Endpoint
- Event-free Survival (EFS)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
A prospective, randomized, open-label, multicenter Phase 3 trial designed to compare the safety and efficacy of Tislelizumab combined with chemotherapy followed by surgery versus up-front surgery in resectable head and neck squamous cell carcinoma.
Investigators
Song Fan, MD
Associate Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Eligibility Criteria
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
- •Measurable disease as per RECIST 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:
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
- •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 -
- •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.
Arms & Interventions
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Tislelizumab（neoadjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Cisplatin （neoadjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Nab-paclitaxel （neoadjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Surgical resection
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Cisplatin（adjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Tislelizumab（adjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Radiation
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Carboplatin (neoadjuvant）
Neoadjuvant Tislelizumab + Reduction of Cycles of Chemotherapy (Arm A)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Carboplatin (adjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Nab-paclitaxel （neoadjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Tislelizumab（neoadjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Cisplatin （neoadjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Surgical resection
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Cisplatin（adjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Tislelizumab（adjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Radiation
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Carboplatin (neoadjuvant）
Neoadjuvant Tislelizumab + Chemotherapy (Arm B)
Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab (IV), dose= 200mg, day=1; Cisplatin (IV), dose=75 mg/m2, or Carboplatin (IV), AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, high risk participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Low risk participants receive 200 mg Tislelizumab Q3W plus radiotherapy as adjuvant therapy.
Intervention: Carboplatin (adjuvant）
Up-front Surgery (Arm C)
Following surgical resection, high risk participants receive chemoradiotherapy as adjuvant therapy. Low risk participants receive radiotherapy as adjuvant therapy.
Intervention: Surgical resection
Up-front Surgery (Arm C)
Following surgical resection, high risk participants receive chemoradiotherapy as adjuvant therapy. Low risk participants receive radiotherapy as adjuvant therapy.
Intervention: Cisplatin（adjuvant）
Up-front Surgery (Arm C)
Following surgical resection, high risk participants receive chemoradiotherapy as adjuvant therapy. Low risk participants receive radiotherapy as adjuvant therapy.
Intervention: Radiation
Up-front Surgery (Arm C)
Following surgical resection, high risk participants receive chemoradiotherapy as adjuvant therapy. Low risk participants receive radiotherapy as adjuvant therapy.
Intervention: Carboplatin (adjuvant）
Outcomes
Primary Outcomes
Event-free Survival (EFS)
Time Frame: Up to 3 years
EFS is the time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence as assessed with imaging or biopsy as indicated; or death due to any cause.
Secondary Outcomes
- Major Pathological Response (MPR) rate(Up to 30 days post-sugery)
- Event-free Survival (EFS)(Up to 5 years)
- Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Adverse Events(From time of first dose of study treatment until the end of follow-up (up to 5 years))
- Pathological complete response (pCR) rate(Up to 30 days post-sugery)
- Objective Response Rate (ORR)(Up to 30 days post-sugery)