Zongertinib, a HER2-directed tyrosine kinase inhibitor, showed promising efficacy and safety in patients with advanced HER2-mutated solid tumors, including non-small cell lung cancer (NSCLC). In the phase 1a/b Beamion LUNG-1 study, zongertinib demonstrated a 30% objective response rate (ORR) and 83% disease control rate (DCR), with a median duration of response of 12.7 months. While the safety profile was generally manageable, 95% of patients experienced any-grade treatment-emergent adverse events (TEAEs), and 10% experienced grade 5 TEAEs. Notably, the FDA granted priority review for zongertinib in HER2-mutant NSCLC, with a target action date of Q3 2025
The drug exhibited responses across multiple tumor types, with patients receiving zongertinib showing significant ORR and DCR in HER2-mutant NSCLC. The study identified 120 mg and 240 mg once-daily doses as recommended for the expansion portion of the trial. Additional safety data revealed common treatment-related adverse events such as diarrhea and rash, but no grade 5 TEAEs. The phase 1a trial results suggest that zongertinib may offer a new treatment option for patients with HER2-altered solid tumors, particularly HER2-mutant NSCLC. Further recruitment into the phase Ib portion is ongoing, and the FDA is expected to decide on approval in late 2025.
Reference: Doherty K. Zongertinib Displays Early Activity and Tolerability in HER2-Mutated Solid Tumors. OncLive. Published March 10, 2025. Accessed March 19, 2025. https://www.onclive.com/view/zongertinib-displays-early-activity-and-tolerability-in-her2-mutated-solid-tumors
