A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 406
- 试验地点
- 135
- 主要终点
- Investigator-Assessed Event-Free Survival (INV-assessed EFS)
研究概览
简要总结
This study will evaluate the efficacy and safety of atezolizumab compared with placebo as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (SCCHN)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients who have received surgery alone or radiotherapy alone as definitive local therapy
- •Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology
- •Evidence of disease progression or metastatic disease during or following definitive local therapy documented in post-definitive local therapy screening scans
- •Uncontrolled or symptomatic hypercalcemia
- •Active or history of autoimmune disease or immune deficiency
- •Active tuberculosis
- •Significant cardiovascular disease
- •History of malignancy, including prior SCCHN primary tumors within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- •Prior allogeneic stem cell or solid organ transplantation
- •Current treatment with anti-viral therapy for Hepatitis B Virus (HBV)
- •Treatment with systemic immunostimulatory agents
- •Treatment with systemic immunosuppressive medication
- •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment
- •Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA, approved agent as part of definitive local therapy, unless the unapproved agent was given in addition to an approved agent
- •Any systemic therapies after permitted definitive local therapies
研究组 & 干预措施
Atezolizumab
Participants will receive Atezolizumab for 16 cycles, or up to 1 year (whichever occurs first)
干预措施: Atezolizumab (Drug)
Placebo
Participants will receive Placebo for 16 cycles, or up to 1 year (whichever occurs first).
干预措施: Placebo (Drug)
结局指标
主要结局
Investigator-Assessed Event-Free Survival (INV-assessed EFS)
时间窗: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.
次要结局
- Overall Survival (OS)(Randomization to death from any cause (up to 5 years, 5 months))
- Independent Review Facility (IRF) Assessed EFS(Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years))
- Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years(From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years)
- Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years(From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years)
- Percentage of Participants Event-Free for OS at 2, 3, and 5 Years(From randomization to OS event or date last known to be alive at 2, 3, and 5 Years)
- Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score(Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years))
- Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score(Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years))
- Number of Participants With at Least One Adverse Event (AE)(From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months))
- Serum Concentration of Atezolizumab(Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year))
- Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab(Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days))