Hernexeos Shows Promise as First-Line Treatment for HER2-mutated Lung Cancer
Promising data presented at the European Society for Medical Oncology (ESMO) Congress in Berlin highlights the potential of Hernexeos (zongertinib) as a first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring HER2 mutations.While currently approved by the FDA for previously treated patients (August 2025, accelerated approval), these results stem from a phase 1b study evaluating the drug in treatment-naïve individuals. A phase 3 randomized controlled trial, Beamion LUNG-2, is now underway to further investigate Hernexeos’ efficacy.
HER2-mutated NSCLC, though representing only 2-4% of all NSCLC cases, is known for its aggressive nature and tendency to metastasize to the brain. The phase 1b trial involved 74 patients, with a small number (two) having received prior treatment. The study population largely consisted of older individuals (58% aged 65 or older) with a significant history of tobacco exposure (35%) and brain metastases (approximately 30%).
The primary endpoint, objective response rate (ORR), demonstrated a substantial 77% response, indicating a measurable reduction in tumor size in a significant portion of patients. Disease control rate reached 96%. responses were observed relatively quickly, with a median time to objective response of 1.4 months.
Further analysis revealed a median follow-up of 9.7 months for duration of response, with an 80% (95% CI, 65%-89%) of patients maintaining a response at six months. Median progression-free survival reached 11.6 months, and the six-month progression-free survival rate was 79%.
While 91% of patients experienced treatment-related side effects,the majority were mild. Grade 3 side effects, representing more significant adverse events on a 1-5 scale, were reported in 18% of patients, with no grade 4 or 5 events observed. Dose reductions were required in 15% of patients due to side effects, and 9% discontinued treatment as a result. Two patients experienced interstitial lung disease/pneumonitis.
Presenting the data, Dr.Sanjay Popat of The Royal Marsden NHS Foundation Trust concluded that “Zongertinib given as a first-line therapy demonstrated significant and clinically meaningful benefit in treatment-naïve patients with advanced HER2-mutant NSCLC.” The benefits of hernexeos treatment were observed across various HER2 mutation types, including the common A775_G776insYVMA mutation, which was present in approximately two-thirds of the study participants.
