An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 454
- 试验地点
- 130
- 主要终点
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
研究概览
简要总结
DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations
详细描述
Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease.
The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
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
- None
入排标准
- 年龄范围
- 18 Years 至 123 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants at least 18 years of age
- •Locally advanced and unresectable NSCLC, not amenable to curative therapy, or metastatic disease
- •Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA
- •Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Measurable disease assessed by Investigator based on RECIST 1.1
- •Protocol-defined adequate organ function including cardiac, renal, hepatic function
- •Having tumour tissue available for central testing
排除标准
- •Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy)
- •Any untreated brain metastases, including asymptomatic or clinically inactive brain metastases
- •Active autoimmune or inflammatory disorders
- •Medical history of myocardial infarction within 6 months prior to randomization
- •History of non-infectious pneumonitis/ILD, current or suspected ILD
- •Lung-specific intercurrent clinical significant severe illness
- •Contraindication to platinum-based doublet chemotherapy or pembrolizumab
研究组 & 干预措施
Arm 1
Trastuzumab Deruxtecan (T-DXd)
干预措施: Trastuzumab Deruxtecan (Drug)
Arm 2
Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)
干预措施: Cisplatin (Drug)
Arm 2
Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)
干预措施: Carboplatin (Drug)
Arm 2
Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)
干预措施: Pemetrexed (Drug)
Arm 2
Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
时间窗: Until progression or death, assessed up to approximately 12 months
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
次要结局
- Overall Survival (OS)(Until death, assessed up to approximately 28 months.)
- Progression Free Survival (PFS) by investigator assessment(Until progression, assessed up to approximately 12 months)
- Objective Response Rate (ORR)(Until progression, assessed up to approximately 12 months)
- Duration of Response (DoR)(Until progression, assessed up to approximately 12 months)
- Safety and tolerability of T-DXd versus Standard of Care treatment(Until progression or death, assessed up to approximately 28 months)
- Patient-reported tolerability of T-DXd described using overall side-effect bother(Until progression, assessed up to approximately 13 months)
- Landmark analysis of PFS (PFS12)(Assessed up to approximately 12 months)
- Landmark analysis of OS (OS24)(Assessed up to approximately 24 months)
- Immunogenicity of T-DXd(Until progression, assessed up to approximately 13 months)
- Time to second progression or death (PFS2)(Assessed up to approximately 20 months)
- Patient-reported tolerability of T-DXd described using symptomatic AEs(Until progression, assessed up to approximately 13 months)
- Patient-reported tolerability of T-DXd described using physical function(Until progression, assessed up to approximately 13 months)
- Central Nervous System (CNS) - Progression Free Survival (PFS)(Until CNS progression or death, assessed up to approximately 12 months)
- Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum(Up to cycle 4, approximately 12 weeks)
- Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer(Until progression, assessed up to approximately 13 months)