Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

Inclusion criteria:

1. Signed and dated written informed consent form (ICF) in accordance withInternational Council for Harmonisation of Technical Requirements forPharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and locallegislation prior to admission to the trial.

2. Patients ≥18 years of age or over the legal age of consent in countries where thatis greater than 18 years at the time of signature of the ICF.

3. Histologically or cytologically confirmed diagnosis of an advanced and/or metastaticnon-squamous Non-small cell lung cancer (NSCLC).

4. Documented Human epidermal growth factor receptor 2 (HER2) mutation in the Tyrosinekinase domain (TKD) as per local lab results.

5. An archival tumor tissue sample must be submitted to the central laboratory afterinclusion of the patient to retrospectively confirm the HER2 status. If no archivaltissue is available, this may be acceptable in exceptional cases after writtenagreement with the sponsor.

6. Patients who have not received any systemic treatment for unresectable, locallyadvanced or metastatic disease and are not eligible for curative therapy.

7. Presence of at least one measurable lesion according to Response evaluation criteriain solid tumors (RECIST) 1.1, as determined by the local site investigator/radiologyassessment.

8. Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab inaccordance with the Summaries of Product Characteristics (SmPC)/Product Information.

Further inclusion criteria apply.

Exclusion criteria:

1. Previous or concomitant malignancies other than the one treated in this trial withinthe last 5 years, except;

• effectively treated non-melanoma skin cancers

• effectively treated carcinoma in situ of the cervix

• effectively treated ductal carcinoma in situ

• other effectively treated malignancy that is considered cured by localtreatment

2. Tumors with targetable alterations with approved available therapy.

3. Lung-specific intercurrent clinically significant severe illness based oninvestigators assessment.

4. Patients who must or wish to continue the intake of restricted medications or anydrug considered likely to interfere with the safe conduct of the trial.

5. Major surgery (major according to the investigator's assessment) performed within 4weeks prior to randomization or planned within 6 months after screening, e.g. hipreplacement.

6. Any history of or concomitant condition that, in the opinion of the investigator,would compromise the patient's ability to comply with the trial or interfere withthe evaluation of the safety and efficacy of the test drug.

7. History or presence of cardiovascular abnormalities such as uncontrolledhypertension, congestive heart failure New York Heart Association (NYHA)classification of ≥ III or IV, unstable angina or poorly controlled arrhythmia whichare considered as clinically relevant by the investigator. Myocardial infarction,stroke, or pulmonary embolism within 6 months prior to randomization.

8. Any clinically important abnormalities (as assessed by the investigator) in rhythm,conduction, or morphology of resting electrocardiograms, e.g. complete left bundlebranch block, third degree heart block.

Further exclusion criteria apply.