Boehringer Ingelheim breaks into oncology as FDA grants accelerated approval to Hernexeos (zongertinib) for HER2 TKD–mutated NSCLC

The FDA granted accelerated approval to Hernexeos (zongertinib) on August 8, 2025 for adults with unresectable or metastatic non-squamous NSCLC whose tumors harbor HER2 (ERBB2) tyrosine kinase domain activating mutations, after prior systemic therapy25.

As part of the approval, the FDA authorized the Oncomine Dx Target Test as a companion diagnostic to identify eligible HER2 TKD mutations in non-squamous NSCLC2.

The decision was supported by the Beamion LUNG-1 trial (NCT04886804); reports cite an objective response rate around 75% in previously treated patients, forming the basis for the accelerated approval35.

Other data cited around the program include Phase I/II results reporting ORR in the range of 48%–66.7% in certain cohorts and intracranial activity, reflecting activity across studies leading up to approval1.

Hernexeos is an oral tyrosine kinase inhibitor and is described as the first oral targeted therapy approved for HER2-mutant NSCLC, entering direct competition with the ADC Enhertu (approved for HER2-mutant NSCLC in 2022)31.

The approval was fast-tracked with priority review and breakthrough therapy designation given the unmet need in the 2%–4% of NSCLC patients with HER2 mutations, who face poorer prognosis and higher brain metastasis risk3.

The approval is contingent on confirmatory evidence of clinical benefit; continued approval may depend on results from ongoing confirmatory trials13.

This marks Boehringer Ingelheim’s entry into oncology after approximately 140 years, signaling a strategic expansion into cancer therapeutics1.

Sources:

1. https://www.biospace.com/drug-development/140-year-old-boehringer-ingelheim-dives-into-cancer-with-nsclc-nod

2. https://oncodaily.com/oncolibrary/zongertinib-for-her2-mutant-nsclc

3. https://www.pharmaceutical-technology.com/news/boehringer-hernexos-fast-track-fda-approval/

5. https://www.pharmexec.com/view/fda-grants-accelerated-approval-boehringer-ingelheim-hernexeos-unresectable-metastatic-non-squamous-non-small-cell-lung-cancer