In this phase 1b multicohort study, first-line zongertinib demonstrated a 76% objective response rate with durable responses and a median progression-free survival of 14.4 months in patients with advanced HER2-mutant NSCLC. The treatment was generally well tolerated, with predominantly low-grade adverse events and a manageable safety profile. Zongertinib also showed intracranial activity in patients with active brain metastases.
Study
|
Phase 1a–1b multicohort trial [Beamion LUNG-1] |
| Previously untreated advanced nonsquamous HER2-mutant NSCLC |
| Zongertinib 120 mg once daily (n=74)
|
Efficacy
|
ORR: 76% (8% CR, 65% PR) |
| mDoR: 15.2 mos [9.8-NE] |
| mPFS: 14.4 mos [11.1-NE] |
| In cohort 4 with active brain metastases: intracranial ORR 47%
|
Safety
|
Grade >=3 TRAEs: increased ALT 4%, decreased ejection fraction 4%, decreased neutrophil count 1%, diarrhea 3%, anemia 3%, increased AST 3%, paronychia 1% |
| Treatment discontinuation due to AEs: 9% |
| Two grade 2 pnuemonitis cases
|
N Engl J Med 2026;394:1675-84
http://doi.org/10.1056/NEJMoa2516969
Reviewed by Ulas D. Bayraktar, MD on May 15, 2026
