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
Study Description
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.
Eligibility
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
Patients must be greater or equal to 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.
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.
