Comparison of the new investigational drug zongertinib with standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with a HER2 mutation

Lung cancer is a malignant disease in which cells in the lungs multiply uncontrollably and can destroy healthy tissue. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and generally grows more slowly than small cell lung cancer. In some patients, the cancer develops due to changes (mutations) in the HER2 gene, which is normally responsible for cell growth. When HER2 is mutated, it constantly signals the cancer cells to grow and multiply, making the tumor more aggressive. In treatment, the HER2 receptor on the cancer cells can be targeted. The standard therapy for locally advanced or metastatic NSCLC, in cases where surgical removal of the tumor is not possible or advisable, depends on specific characteristics of the tumor. In such cases, factors such as genetic alterations (EGFR, ALK, HER2, etc.) or PD-L1 status—which indicates response to immunotherapy—are decisive. In other types of tumors, the HER2 receptor is already used as a target for first-line targeted therapies—but this has not yet been the case for NSCLC. The standard of care for NSCLC typically involves a combination of chemotherapy (usually platinum- and pemetrexed-based) and immunotherapy (e.g., pembrolizumab) to destroy cancer cells and strengthen the immune system. A new approach involves the use of the targeted drug zongertinib. It specifically targets the HER2 receptor on cancer cells, thereby blocking their growth. However, it has not yet been approved for use outside of clinical trials.

The goal of the BEAMION Lung-2 study is to investigate the efficacy and safety of targeted therapy with zongertinib and to compare it with the standard of care for NSCLC tumors with specific mutations in the HER2 gene.

To this end, patients will be randomly assigned to two groups (arms). Patients in the first arm (treatment arm) will receive the new, as-yet-unapproved drug zongertinib. The drug is taken as a tablet. Patients in the second arm of the study (control arm) will receive the current standard therapy, consisting of immunotherapy with pembrolizumab and platinum- and pemetrexed-based chemotherapy. Treatment is administered as an intravenous infusion. In both arms, treatment continues until the cancer progresses or patients no longer derive any benefit from the treatment. Afterward, patients will continue to be monitored as part of the study for up to six years. Assignment to the two study arms is open-label, meaning that both patients and treating physicians know which arm of the study they have been assigned to.

Women and men aged 18 and older who have locally advanced or metastatic NSCLC are eligible to participate in the study. In these cases, surgical removal of the tumor must no longer be possible or advisable (inoperable), and the tumor must be HER2-positive. No prior systemic treatment may have been administered.