Multinational phase 1a trial of zongertinib for advanced solid tumors with HER2 alterations

Zongertinib (BI 1810631) is a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor. The multinational phase 1a Beamion LUNG-1 study evaluated zongertinib in patients with advanced or metastatic NSCLC (n=54) or other solid tumors (n=51) with HER2 alterations. The recommended doses for expansion were 120 mg twice daily and 240 mg once daily. Treatment-related adverse events were seen in 82% of patients; grade ≥3 TRAEs occurred in 10%. The confirmed investigator-assessed overall response rate across all doses and tumors was 30% (95% CI 23-40) with median duration of response 12.7 months (6.9-NR); among the NSCLC patients the confirmed ORR was 35% (22-49). Activity was observed in patients who previously received HER2-directed therapy (ORR 28%). Among NSCLC patients receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI 8.3-NR). The authors conclude that zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with advanced HER2-altered tumors, including NSCLC.