Study
| Multicohort, open-label, phase 1a–1b trial (Beamion LUNG-1, NCT04886804) |
| Previously treated advanced or metastatic HER2-mutant NSCLC |
| Zongertinib 120 mg daily (selected dose) in patients with HER2 TKI-domain mutations (cohort 1), HER2 TKI-domain mutations after antibody-drug conjugate (cohort 5), and non-TKI HER2 mutations (cohort 3) |
Efficacy
| ORR: 71% (cohort 1), 48% (cohort 5), 30% (cohort 3) |
| CR: 7% (cohort 1) |
| mDoR: 14.1 mos (cohort 1), 5.3 mos (cohort 5) |
| mPFS: 12.4 mos (cohort 1) |
| ORR in cohort 1 with brain mets: 64% |
| Intracranial ORR (RANO-BM): 41% |
Safety
| Grade ≥3 drug-related AEs: 17% (cohort 1), 3% (cohort 5), 25% (cohort 3) |
| Common AEs: diarrhea (56%; G3 in 1%), rash (33%; all ≤ G2), elevated liver enzymes (AST 5%, ALT 8%) |
| Drug-related ILD: none |
| Discontinuation due to AEs: 3% |
| Dose reductions: 7% |
N Engl J Med 2025;390:1337-47
Heymach JV,Ruiter G,Ahn MJ Zongertinib in Previously Treated HER2-Mutant Non–Small-Cell Lung Cancer
http://doi.org/10.1056/NEJMoa2503704
Reviewed by Ulas D. Bayraktar, MD on May 5, 2025
