Among patients with untreated, advanced HER2-mutated non-small cell lung cancer (NSCLC), treatment with Hernexeos (zongertinib) was associated with a significant and clinically meaningful benefit, clinical trial results have shown.
Results from the phase 1 Beamion LUNG-1 trial were presented at the European Society for Medical Oncology Congress 2025.
The objective response rate (ORR) was 77%, with a complete response rate of 8% and a partial response rate of 69%. The disease control rate was 96% with a stable disease rate of 19% and a progressive disease rate of 1%.
The median time to objective response was 1.4 months, and at the time of data cutoff, 47% of patients remained on treatment.
The median follow-up for duration of response (DOR) was 9.7 months, and the six-month DOR rate was 80%. The median follow-up for progression-free survival (PFS) was 11.6 months, and the six-month PFS rate was 79%.
“[Hernexeos] given as a first-line therapy demonstrated significant and clinically meaningful benefit in treatment-naïve patients with advanced HER2-mutant NSCLC,” Sanjay Popat, consultant medical oncologist, head of the Lung Unit, and lead for the Lung Cancer Research Programme at The Royal Marsden NHS Foundation Trust, stated during the presentation.
A total of 74 patients were given 120 mg of Hernexeos. Of note, two patients had received prior treatment. The presentation focused on cohort 2, which enrolled patients who were treatment-naïve and had a tyrosine kinase domain (TKD) mutation.
Patients were included if they were 18 years or older with advanced/metastatic non-squamous HER2-mutated NSCLC with one or more measurable non-central nervous system lesions, and an ECOG performance status of 0 or 1. Additionally, patients who had stable/asymptomatic brain metastases were eligible for treatment.
The median patient age was 67 years, 40% of patients were between 65 and 74 years old, and 18% were 75 years or older. Additionally, 46% of patients were Asian compared with 45% who were not, 64% of patients had never used tobacco, 30% had brain metastases, and 66% had A775_G776insYVMA.
Regarding safety, 91% of patients reported treatment-related side effects, with 18% reporting a grade 3 (severe) treatment-related side effect. No grade 4 (life-threatening) or 5 (fatal) treatment-related side effects were reported. A total of 15% of patients had side effects leading to dose reductions, and 9% had side effects leading to discontinuation. There were two cases of interstitial lung disease/pneumonitis, both of which were grade 2.
The most common TRAEs included diarrhea (54%), rash (23%), alanine aminotransferase increased (18%), aspartate aminotransferase increased (16%), dysgeusia (16%), and nausea (16%). Popat noted that the safety profile remained consistent with previously reported data. Additionally, there was a low incidence of grade 3 or higher side effects.
In August 2025, the FDA gave accelerated approval to Hernexeos for patients with previously treated metastatic or unresectable non-squamous NSCLC who had HER2 TKD activating mutations, as detected by an FDA-approved test.2
References
- “Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG-1,” by Sanjay Popat, et al. Presented at the European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA74.
- “FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations,” FDA; https://tinyurl.com/bdh2d4uc
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