A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Participants With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 370
- 试验地点
- 127
- 主要终点
- Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set
研究概览
简要总结
This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in Participants with recurrent or metastatic head and neck cancer
详细描述
Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who had prior immune checkpoint inhibitor and platinum-based chemotherapy treatment will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab. Efficacy and safety assessments will be performed periodically from the time of enrollment and throughout the study. Participants in all arms will continue therapy until progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. All Participants will be followed for survival after progression is confirmed.
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)
盲法说明
Double blinded study
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are aged 18 years and over
- •Recurrent or metastatic squamous cell carcinoma of the SCCHN, oral cavity, oropharynx, hypopharynx, or larynx which has progressed on or after previous systemic cancer therapy and is not amenable to curative therapy
- •Received prior treatment using a programmed cell death ligand-1 (PD-L1) inhibitor
- •Prior platinum failure
- •Received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN
- •Has measurable disease per RECIST 1.1
- •A fresh or recently acquired tumor tissue for the purpose of biomarker testing
- •World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
排除标准
- •Head and neck cancer of any primary anatomic location in the head and neck not specified in the inclusion criteria, including participants with SCCHN of unknown primary or non-squamous histologies
- •Had prior cetuximab therapy (unless it was administered in curative locally advanced setting with radiotherapy and no disease progression for at least 6 months following the last cetuximab dose)
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis
- •Any concurrent anticancer treatment, except for hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy)
研究组 & 干预措施
Placebo Q2W + Cetuximab 400 mg/m^2
Participants will receieve IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
干预措施: Cetuximab (Drug)
Placebo Q2W + Cetuximab 400 mg/m^2
Participants will receieve IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
干预措施: Placebo (Other)
Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2
Participants will receive intravenous (IV) monalizumab 750 mg every two weeks (Q2W) and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 every one week (Q1W) until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
干预措施: Cetuximab (Drug)
Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2
Participants will receive intravenous (IV) monalizumab 750 mg every two weeks (Q2W) and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 every one week (Q1W) until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
干预措施: Monalizumab (Drug)
结局指标
主要结局
Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set
时间窗: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and hazard ratio (HR) and confidence intervals (CIs) from a stratified Cox proportional hazards model. Analyses were stratified on World Health Organization/ Eastern Cooperative Oncology Group performance status (WHO/ECOG PS) (0 or 1) and number of prior lines of therapy in recurrent or metastatic (R/M) setting (1 or 2).
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 through 21.4 months (maximum observed duration))
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 1 through 21.4 months (maximum observed duration))
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 through 21.4 months (maximum observed duration))
- Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Duration of Response (DoR) Per RECIST 1.1 in HPV-unrelated Analysis Set(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Overall Survival in Full Analysis Set (FAS)(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Percentage of Participants With OR Per RECIST 1.1 in FAS(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Duration of Response Per RECIST 1.1 in FAS(Baseline (-28 to -1) through 17.5 months (maximum observed duration))
- Number of Participants With Electrocardiograms (ECGs) Reported as TEAEs(Day 1 through 21.4 months (maximum observed duration))