The FDA granted accelerated approval to Boehringer Ingelheim’s Hernexeos (zongertinib), the first oral targeted therapy for adults with HER2-mutant advanced non-small cell lung cancer (NSCLC) who have previously received other treatments.
The approval applies to patients with advanced non-squamous NSCLC that has spread and whose tumors carry specific changes in the HER2 protein, caused by alterations in the ERBB2 gene, that affect the protein’s tyrosine kinase domain. These changes must be confirmed by an FDA-approved test.
The decision was based on results from the Phase Ib Beamion-LUNG 1 trial and followed the FDA’s Priority Review and Breakthrough Therapy designation. Continued approval will depend on further trial results confirming clinical benefit.
The FDA also approved Thermo Fisher’s Oncomine Dx Target Test as the companion diagnostic for this indication. The next-gen sequencing test detects HER2 (ERBB2) mutations in the tumor’s tyrosine kinase domain, helping identify patients most likely to benefit from treatment.
NSCLC accounts for about 85% of lung cancer cases worldwide. Within this group, HER2 mutations are relatively rare — about 2% to 4% of cases — but are linked to a higher risk of brain metastases and generally poorer outcomes. These mutations are most often seen in people with adenocarcinoma, commonly in women and those who have never smoked, and they rarely occur alongside other targetable mutations.
Advanced NSCLC is often diagnosed at a late stage, with a historical five-year survival rate of less than 10%.
XTALKS WEBINAR: Unlocking Oncology Pipelines with Next-Gen AI and Functional Data
Live and On-Demand: Wednesday, September 3, 2025, at 11am EDT (5pm CEST/EU-Central)
Register for this free webinar to learn how functional multi-omic data and AI integration can accelerate cancer target discovery.
What Is a Tyrosine Kinase Inhibitor?
Tyrosine kinase inhibitors (TKIs) are targeted cancer drugs that block the “on switches” driving tumor growth and spread. They are most often used in breast cancer, NSCLC, chronic myeloid leukemia and kidney cancer.
Zongertinib is a TKI designed to block HER2 activity and interrupt cancer cell growth signals. It is taken as a once-daily pill, with the dose based on body weight, and can be taken with or without food until the cancer progresses or side effects become unacceptable.
Clinical Trial Outcomes Supporting Hernexeos’ Approval
In Beamion-LUNG 1, 71 patients who had received prior platinum-based chemotherapy but no HER2-targeted treatment achieved an objective response rate of 75%, including complete responses in 6% and partial responses in 69%. More than half (58%) had a response lasting at least six months.
In a separate group of 34 patients who had also received a HER2-targeted antibody-drug conjugate, the response rate was 44%, with 27% maintaining responses for six months or longer.
The most common side effects, seen in over 20% of patients, were diarrhea, liver toxicity, rash, fatigue and nausea. More serious risks include liver damage, reduced heart function and lung inflammation.
The drug offered meaningful responses for a patient group with few targeted options and had a manageable safety profile. Boehringer is also studying zongertinib in other HER2-altered cancers.
Related: Zegfrovy Gets FDA Nod as New Oral Option After Chemo for EGFR Ex20Ins NSCLC
The Tyrosine Kinase Market, Key Players & Other Updates in NSCLC
TKIs are a core part of precision medicine, used for cancers with known genetic changes. The global TKI market was worth $68.21 billion in 2025 and is expected to grow to $96.02 billion by 2030. Major developers include AstraZeneca, Novartis, AbbVie, Pfizer, Roche, Bristol Myers Squibb, Bayer, Boehringer Ingelheim and Johnson & Johnson.
Recent NSCLC updates include:
- Taletrectinib (Ibtrozi, Nuvation Bio): FDA-approved for ROS1-positive NSCLC, with proven effectiveness against brain metastases
- Ivonescimab (Summit Therapeutics/Akeso): A dual-action antibody blocking PD-1 and VEGF, now in Phase III NSCLC trials, including for EGFR-mutant and PD-L1-high disease
- VS-7375 (Verastem Oncology): An oral drug targeting KRAS G12D mutations, in early-phase trials for multiple solid tumors, with planned combinations in NSCLC
- Fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo/AstraZeneca): Approved in several cancers, with a recent Breakthrough Therapy designation for HER2-mutant NSCLC
Beyond NSCLC, TKIs are increasingly used alongside other treatments to delay resistance and extend benefit.
If you want your company to be featured on Xtalks.com, please email [email protected].
Join or login to leave a comment
JOIN LOGIN