This is a multi-regional, multi-centre, open-label, randomized, active-controlled, parallel-group Phase III trial of orally administered zongertinib (BI 1810631) versus SoC (intravenous pembrolizumab combined with platinum-pemetrexed chemotherapy

Zongertiib (BI 1810631) 120 mg oral vs pembrolizumab plus platinum pemeterexed chemotherapy

Main inculsion criteria: zie protocol voor full version:
Main inclusion criteria

• Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF).
• Histologically or cytologically confirmed diagnosis of advanced and/or metastatic non-squamous NSCLC.
• Documented HER2 mutation in the TKD as per local lab results preferably by tissue NGS/PCR, but also ctDNA.
• Availability and willingness to provide a sample of archival formalin-fixed paraffin embedded (FFPE) tumor tissue material. Patients who have not received any systemic treatment for locally advanced or metastatic disease. Prior neoadjuvant and/or adjuvant chemotherapy or immunotherapy is allowed if the treatment was completed more than 6 months prior to trial entry.
• Presence of at least one measurable lesion according to RECIST 1.1, as determined by the local site investigator/radiology assessment. Patients with asymptomatic (i.e. no clinical [neurological] symptoms) brain lesions are eligible.
• Eligible to receive treatment with the selected platinumbased doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the Summary of Product Characteristics/Product Information.
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Adequate organ function based on laboratory values

Main exclusion criteria: voor volledige versie zie protocol:

• Tumors with targetable alterations with approved available therapy.
• Presence or history of uncontrolled or symptomatic brain, subdural metastases or leptomeningeal disease, unless considered stable by the investigator and local therapy was completed.
• Lung-specific intercurrent clinically significant severe illness based on investigators assessment
• Radiotherapy within 4 weeks prior to randomization with exception of palliative radiotherapy completed 2 weeks prior to randomization. Major surgery (major according to the investigator’s assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening.
• 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 with the evaluation of the safety and efficacy of the test drug.
• History or presence of cardiovascular abnormalities which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization.
• Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms.
• Mean resting corrected QT interval (QTcF) >470 msec.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-ofage, or any concomitant medication known to prolong the QT interval.
• Ejection fraction <50% or the lower limit of normal of the institutional standard, whatever is lower.
• Active or known pre-existing non-infectious interstitial lung disease/pneumonitis.
• Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug in the opinion of the investigator