Zongertinib Nabs FDA Approval in Nonsquamous HER2 TKD+ NSCLC

The FDA has approved Oncomine Dx Target Test alongside zongertinib.

The FDA has granted accelerated approval to zongertinib (Hernexeos) for use in patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations who have received at least 1 prior systemic therapy.

Along with this approval, the FDA approved the Oncomine Dx Target Test as a companion diagnostic device in order to identify HER2 (ERBB2) TKD activating mutations in patients who may be eligible for treatment with zongertinib.

What Data Led to Zongertinib’s Approval?

The efficacy of zongertinib was assessed in the above patient population in the open-label, multicenter, multicohort Beamion LUNG-1 trial (NCT04886804). The primary end points were objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR).

Out of 71 patients who had received previous platinum-based chemotherapy and no HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate (ADC), the ORR was 44% (95% CI, 29%-61%) and the 6-month-or-longer DOR occurred in 27% of patients.

Zongertinib’s dose is based on body weight, dictating that patients weighing under 90 kg should receive 120 mg of zongertinib orally once daily, and patients weighing 90 kg or more should receive 180 mg of zongertinib orally once daily. It may be taken with or without food and should be discontinued upon disease progression or unacceptable toxicity.

Warnings for hepatotoxicity, left ventricular dysfunction, interstitial lung disease (ILD)/pneumonitis, and embryo-fetal toxicity are included in zongertinib’s prescribing information.

Previous Beamion LUNG-1 Analysis Data

Data from Beamion LUNG-1 published in the Journal of Clinical Oncology in March 2025 revealed that treatment-related adverse events (TREAs) of any grade occurred in 82% of patients. Grade 3 or higher TRAEs occurred in 10% of patients.

The most common any-grade TRAEs were diarrhea (50%), rash (16%) anemia (10%), decreased appetite (10%), and increased alanine transaminase (ALT; 4%). Likewise, those TRAEs were grade 3 or higher in 1%, 2%, 0%, 1%, and 4% of patients, respectively.

This analysis also revealed a median progression-free survival (PFS) of 17.2 months (95% CI, 8.3-NR).

References

1. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed August 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations
2. Heymach JV, Opdam F, Barve M, et al. HER2-selective tyrosine kinase inhibitor, zongertinib (BI 1810631), in patients with advanced/metastatic solid tumors with HER2 alterations: a phase Ia dose-escalation study. J Clin Oncol. 2025;43(11):1337-1347. doi:10.1200/JCO-24-01727