Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutations

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.