Zongertinib’s Efficacy, Safety in HER2-Mutant NSCLC

In an interview with Targeted Oncology, Gerrina Ruiter, MD, PhD, Netherlands Cancer Institute, highlights key efficacy and safety data from the phase 1 Beamion LUNG-1 study (NCT04886804) evaluating zongertinib (Hernexeos) in human epidermal growth factor receptor 2 (HER2)-mutant non–small cell lung cancer (NSCLC), reflecting on potential treatment implications.

Watch the first part of Dr Ruiter’s interview.

Safety data from the trial were previously published in The New England Journal of Medicine in April 2025.¹ In the most recent readout of data at the IASLC 2025 World Conference on Lung Cancer (WCLC), no new safety signals were reported.

Zongertinib demonstrated promising activity in the brain during the dose-expansion stage, achieving an objective response rate (ORR) of 41% per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM). Additionally, in terms of secondary end point measures, the data revealed a high disease control rate of 83% and a median progression-free survival of 8.2 months.

The most salient takeaway from the data, according to Ruiter, is the evidence of zongertinib’s intracranial activity, as there is currently no other HER2 tyrosine kinase inhibitor that has demonstrated a response in the brain.

“HER2-mutated lung cancer is rare, but brain metastasis is highly prevalent in these patients. Fifty percent of patients who have HER2-mutant [NSCLC] develop brain metastases during their lifetime. This means that despite new treatments developing [for NSCLC], one [being] zongertinib, it is also important to see that these drugs work for brain metastases,” Ruiter said in the interview.

“I think the fact that zongertinib works in the brain is the major finding, because we did not know that, and we do not have any HER2 TKI so far that has demonstrated [an] effect in the brain. So, this is really important to show—that this drug not [only] has a high systemic response rate but also induces responses in the brain,” Ruiter added.

Read the full interview here.

REFERENCES:

1. Heymach JV, Ruiter G, Ahn MJ, et al. Zongertinib in Previously Treated HER2 -Mutant Non–Small-Cell Lung Cancer. N Engl J Med. 2025;392(23):2321–2333. doi:10.1056/nejmoa2503704