Beamion LUNG-3: A Randomized, Controlled, Multi-center Trial Evaluating Zongertinib as an Adjuvant Monotherapy Compared With Standard of Care in Patients With Early-stage, Resectable Non-small Cell Lung Cancer (Stage II-IIIB) Harboring Tyrosine Kinase Domain Activating HER2 Mutations
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 362
- 主要终点
- Disease-free survival (DFS) by investigator's assessment
研究概览
简要总结
Beamion LUNG-3 study evaluates whether zongertinib, an oral HER2-targeted treatment, can improve outcomes compared with standard adjuvant treatment in adults with completely resected Stage II-IIIB non-small cell lung cancer (NSCLC) whose tumors have activating HER2 tyrosine kinase domain (TKD) mutations. Eligible participants must have undergone curative-intent surgery and received guideline-appropriate perioperative systemic therapy, either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy.
Participants are randomized 1:1 to receive zongertinib or standard of care, which may consist of approved adjuvant immunotherapy or active surveillance, based on local practice guidelines. The main purpose of the study is to determine whether zongertinib can prolong disease-free survival compared to standard treatment. Safety and patient-reported outcomes are also assessed.
详细描述
This is a global, randomized, open-label, Phase 3 study designed to assess the efficacy and safety of zongertinib as adjuvant therapy in participants with completely resected Stage II-IIIB NSCLC and HER2 TKD-activating mutations.
Participants must have undergone complete resection and received perioperative systemic therapy consistent with current standards, including either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy.
After completing surgery and required systemic treatment, eligible participants are randomized 1:1 to receive either Zongertinib taken orally once daily for up to 3 years, or standard treatment, which may include an approved adjuvant immunotherapy agent administered according to its label, or observation, depending on local clinical practice and patient status.
The primary objective is to evaluate whether zongertinib improves disease-free survival (DFS) compared with standard treatment. Secondary objectives include overall survival (OS), safety, tolerability, and patient-reported outcomes.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- •Patients must be ≥18 years old or over the legal age of consent in their country
- •Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use dual highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information and in the study protocol
- •HER2 mutation: Documented Tyrosine kinase domain (TKD) activating Human epidermal growth factor receptor 2 (HER2) mutations
- •Histology and tumor sample: Histologically confirmed diagnosis of primary NSCLC
- •An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status
- •Staging: Pretherapeutic classification not exceeding Stage IIIB
- •Performance status and organ function:
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
- •Adequate organ function based on laboratory values Further inclusion criteria apply.
排除标准
- •Diagnosis of NSCLC with mixed histology/positive neuroendocrine markers (synaptophysin/CD56)
- •Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization
- •Treatment with radiation therapy for primary NSCLC
- •Co-occurring actionable mutation with approved targeted therapy (e.g. Epidermal growth factor receptor (EGFR) or Anaplastic lymphoma kinase (ALK))
- •Any investigational drug within 5 half-lives of the compound or any of its related material, if known
- •History or presence of
- •Active or known pre-existing or history of non-infectious interstitial lung disease/pneumonitis
- •Active infectious disease requiring systemic therapy
- •Uncontrolled gastrointestinal disorders affecting drug intake/absorption
- •Previous or concomitant malignancies within the last 3 years, except certain effectively treated cancers
- •Significant and/or uncontrolled cardiovascular abnormalities, QT interval corrected for heart rate by Fridericia formula (QTcF) >470 msec, or ejection fraction <50% Further exclusion criteria apply.
研究组 & 干预措施
Standard of Care (SoC) treatment arm
干预措施: Atezolizumab (Drug)
Standard of Care (SoC) treatment arm
干预措施: Durvalumab (Drug)
Standard of Care (SoC) treatment arm
干预措施: Nivolumab (Drug)
Standard of Care (SoC) treatment arm
干预措施: Pembrolizumab (Drug)
Zongertinib treatment arm
干预措施: Zongertinib (Drug)
结局指标
主要结局
Disease-free survival (DFS) by investigator's assessment
时间窗: up to 8 years and 5 months
DFS is defined as the time from randomization until recurrence of tumor or death from any cause, whichever occurs earlier
次要结局
- Key secondary endpoint: Overall survival (OS), defined as the time from randomization until death from any cause(up to 8 years and 5 months)
- Occurrence of trial-related Adverse Events (AEs) ≥ Grade 3 from first treatment administration (or from randomization for patients in the observation arm) until the earliest of tumor recurrence or 3 years since treatment start(up to 3 years)