Dr Baik on the Clinical Utility of Zongertinib in Previously Treated HER2-Mutant NSCLC

Christina S. Baik, MD, MPH, physician, associate professor, Clinical Research Division, Fred Hutchinson Cancer Center; clinical research director, Thoracic, Head and Neck Oncology, associate professor, Division of Hematology and Oncology, University of Washington School of Medicine, discusses the clinical utility of zongertinib (BI 1810631) in patients with previously treated non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) mutations. She went on to highlight the investigation of the agent in cohort 1 of the phase 1b Beamion LUNG-1 trial (NCT04886804), as well as the ongoing Beamion phase 3 LUNG-2 trial (NCT06151574).

There is still much to learn about zongertinib, particularly in patients with previously treated NSCLC, Baik begins. Current insights come primarily from data in the Beamion LUNG-1 trial and reveal that the adverse effects (AEs) associated with zongertinib appear to be dose dependent, she explains. As seen with other TKIs, dose reduction can often alleviate AEs, such as severe diarrhea, Baik says. She notes that although the severity of AEs varies among patients, dose adjustments have generally shown effectiveness in improving the tolerability of zongertinib.

The Beamion LUNG-2 trial includes a cohort evaluating zongertinib in treatment-naive patients with HER2-mutant NSCLC to explore whether it may outperform the current standard of care (SOC), which consists of chemotherapy combined with immunotherapy, she continues. There is still uncertainty regarding the efficacy of immunotherapy for patients with HER2-mutated NSCLC compared with patients without HER2 mutations or other oncogenic drivers, Baik reports. However, chemoimmunotherapy remains a SOC in the NSCLC treatment paradigm, which is why the control arm of this trial involves chemoimmunotherapy, according to Baik.

The trial’s results are expected to provide clarity on zongertinib’s potential as a first-line treatment for HER2-mutated NSCLC, Baik expands. These data will help define zongertinib’s role compared with current SOCs and clarify whether it can serve as a viable initial treatment option. The findings from this study are highly anticipated as they could establish zongertinib as a significant therapeutic option in the first-line setting for this patient population, she concludes.