A Phase II, Randomized, Double Blind Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Patients With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 87
- 主要终点
- Percentage of Participants With Confirmed Objective Response, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.
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
- •Histologically or cytologically confirmed recurrent/metastatic SCCHN involving the oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local therapies
- •Known results from human papillomavirus (HPV) status test for oropharyngeal carcinoma
- •No prior systemic therapy for metastatic and/or recurrent SCCHN
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Tumor PD-L1 expression as determined by PD-L1 immunohistochemistry assay
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy >=12 weeks
排除标准
- •Disease suitable for local therapy with curative intent
- •Progressive or recurrent disease within 6 months of the last dose of curative intent systemic treatment for locally advanced SCCHN
- •Rapidly progressing disease in the opinion of the treating investigator
- •Grade >=2 unresolved toxicity related to surgery or other prior therapies
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •History of leptomeningeal disease
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •History of additional malignancy other than SCCHN within 5 years prior to randomization
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents or systemic immunosuppressive medication
- •Pregnancy or breastfeeding
研究组 & 干预措施
Atezolizumab + Placebo
Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle.
干预措施: Placebo (Drug)
Atezolizumab + Tiragolumab
Participants will receive atezolizumab followed by tiragolumab every three weeks (Q3W) on Day 1 of each 21-day cycle.
干预措施: Tiragolumab (Drug)
Atezolizumab + Tiragolumab
Participants will receive atezolizumab followed by tiragolumab every three weeks (Q3W) on Day 1 of each 21-day cycle.
干预措施: Atezolizumab (Drug)
Atezolizumab + Placebo
Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Objective Response, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
时间窗: Up to approximately 30.6 months
A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
次要结局
- Duration of Response (DOR)(From first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 30.6 months))
- Progression-free Survival (PFS)(From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 30.6 months))
- Overall Survival (OS)(From randomization to death from any cause (up to approximately 30.6 months))
- PFS Rate at 6 Months(Month 6)
- OS Rate at 6 Months and 12 Months(Months 6 and 12)
- Time to Confirmed Deterioration (TTCD) in Participant-reported Physical Functioning (PF), as Measured by the Patient-reported Outcomes Measurement Information System (PROMIS) Item Bank Version 2.0 (v2.0)-PF-Short Form 10b(Up to approximately 30.6 months)
- Number of Participants With Adverse Events (AEs)(From study start up to 90 days after last dose (up to approximately 52.9 months))
- Serum Concentration of Atezolizumab at Specified Timepoints(Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/early discontinuation (ED) (1 Cycle=21 days) (up to approximately 49.9 months))
- Serum Concentration of Tiragolumab at Specified Timepoints(Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/ED (1 Cycle=21 days) (up to approximately 49.9 months))
- Number of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab(Up to approximately 49.9 months)
- Number of Participants With ADAs to Tiragolumab(Up to approximately 49.9 months)