Frontline zongertinib produced high activity in treatment-naïve, advanced HER2-mutated non-small cell lung cancer (NSCLC) in the phase 1 Beamion LUNG-1 trial presented at the 2025 ESMO Congress: objective response rate 77% (8% complete, 69% partial) and disease control rate 96%, with a median time to response of 1.4 months. Median progression-free survival (PFS) was 11.6 months (6-month PFS, 79%), and the 6-month duration-of-response rate was 80%; 47% of patients remained on treatment at data cutoff. Clinical benefit was observed across HER2 mutation types, including patients with stable brain metastases, and most had A775_G776insYVMA insertion. Together, the speed, depth, and durability of responses highlight zongertinib’s robust antitumor activity in the first-line setting.
Safety was manageable: 91% experienced treatment-related adverse events, largely grade 1 to 2. Grade 3 events occurred in 18%, with no grade 4 to 5 events reported. Common events were diarrhea (54%), rash (23%), elevated alanine aminotransferase/aspartate aminotransferase (18%/16%), dysgeusia (16%), and nausea (16%). Dose reductions and discontinuations occurred in 15% and 9%, respectively, and there were two grade 2 cases of interstitial lung disease/pneumonitis. In August 2025, the FDA granted accelerated approval to zongertinib for previously treated metastatic or unresectable HER2 TKD–mutated NSCLC. These frontline data suggest potential to expand its role earlier in the treatment pathway.
Reference: Pelosci A. Zongertinib Displays Activity in Frontline HER2-Mutated NSCLC. OncLive. Published October 17, 2025. Accessed October 27, 2025. https://www.onclive.com/view/zongertinib-displays-activity-in-frontline-her2-mutated-nsclc
Link: https://www.onclive.com/view/zongertinib-displays-activity-in-frontline-her2-mutated-nsclc
