NCT03505710终止2 期
A Phase 2, Multicenter, Open-Label, 2-Cohort Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2 Antibody Drug Conjugate (ADC), for HER2-Over-Expressing or -Mutated, Unresectable and/or Metastatic Non Small Cell Lung Cancer (NSCLC) (DESTINY-Lung01)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 181
- 试验地点
- 21
- 主要终点
- Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
研究概览
简要总结
The primary objective of this trial is to evaluate the efficacy of trastuzumab deruxtecan in HER2-overexpressing and/or HER2-mutated advanced NSCLC participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥20 years old in Japan, ≥18 years old in other countries
- •Pathologically documented unresectable and/or metastatic non-squamous NSCLC
- •Has relapsed from or is refractory to standard treatment or for which no standard treatment is available
- •For Cohort 1 and Cohort 1a: HER2-overexpression (IHC 2+ or 3+) status must be assessed and confirmed by Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or equivalent, from an archival tumor tissue sample
- •For Cohort 2 only: Participant has any known documented activating HER2 mutation from an archival tumor tissue sample analyzed by CLIA laboratory or equivalent. Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment.
- •Presence of at least 1 measurable lesion assessed by the investigator and based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Is willing and able to provide an adequate archival tumor tissue sample
- •Is willing to undergo a tissue biopsy, after the completion of the most recent treatment regimen
- •Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
排除标准
- •Had been previously treated with HER2-targeted therapies, except for pan-HER class tyrosine kinase inhibitors
- •For Cohort 1 and Cohort 1a: Has known HER2 mutation
- •Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
- •Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out due to imaging at screening
- •Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to > 450 millisecond (ms) in males and > 470 ms in females
- •Has a medical history of clinically significant lung disease
- •Is suspected to have certain other protocol-defined diseases based on imaging at screening period
- •Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
- •safety or well-being of the participant or offspring
- •safety of study staff
- •analysis of results
研究组 & 干预措施
Cohort 1: HER2 Overexpressing
Experimental
Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).
干预措施: Trastuzumab deruxtecan (Drug)
Cohort 1a: HER2 Overexpressing
Experimental
Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).
干预措施: Trastuzumab deruxtecan (Drug)
Cohort 2: HER2 Mutated
Experimental
Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).
干预措施: Trastuzumab deruxtecan (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
时间窗: From screening, up to 36 months (data cut-off)
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported.
次要结局
- Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)(From screening, up to 36 months (data cut-off))
- Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)(From screening to documented tumor progression or death from any cause, up to 36 months (data cut-off))
- Progression-Free Survival (PFS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)(From date of enrollment to first objective radiographic tumor progression or death from any cause,, up to 36 months (data cut-off))
- Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)(From date of enrollment to death from any cause, up to 36 months (data cut-off))
- Percentage of Participants With Disease Control Rate (DCR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)(From first dose, up to 36 months (data cut-off))
研究者
研究点 (21)
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相关资讯
Trastuzumab Deruxtecan's Expanding Role in HER2-Expressing Solid Tumors- Trastuzumab deruxtecan (T-DXd) received FDA approval for HER2-positive solid tumors, marking a significant expansion beyond breast, lung, gastric, and colorectal cancers.
- Clinical trials like DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 demonstrated T-DXd's efficacy across various tumor types, especially those with high HER2 expression.
- T-DXd treatment requires careful monitoring due to potential adverse events like interstitial lung disease (ILD), necessitating proactive management strategies.
- The DEBBRAH trial showed promising antitumor activity of T-DXd in HER2+ and HER2-low advanced breast cancer patients with leptomeningeal disease (LMD), warranting further investigation.last yearTrastuzumab Deruxtecan Shows Promise in HER2-Mutated NSCLC- Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with previously treated HER2-mutated non-small cell lung cancer (NSCLC).
- The DESTINY-Lung01 trial showed a 55% objective response rate in HER2-mutated NSCLC patients treated with T-DXd at 6.4 mg/kg.
- A lower dose of T-DXd (5.4 mg/kg) was approved by the FDA in 2022 for HER2-mutant NSCLC due to comparable efficacy and reduced toxicity.
- Ongoing research explores the potential of T-DXd as a frontline therapy for HER2-overexpressing or mutated NSCLC.last yearEnhertu Shows Promise in Frontline HER2-Mutated NSCLC Treatment• Fam-trastuzumab deruxtecan-nxki (Enhertu) is under investigation as a first-line treatment for HER2-mutated and -overexpressing non-small cell lung cancer (NSCLC).
• The DESTINY-Lung01 trial revealed a 55% objective response rate and a median progression-free survival of 8.2 months in HER2-mutated NSCLC patients.
• Combining ADCs with other agents like immunotherapy or chemoimmunotherapy is being explored, with ongoing trials monitoring overlapping toxicities like cytopenia and ILD.
• Antibody-drug conjugates (ADCs) are demonstrating increasing efficacy in NSCLC, potentially shifting treatment paradigms in both second-line and first-line settings.last year