First-line targeted therapy shows antitumor activity in patients with advanced lung cancer
MD Anderson Research News April 16, 2026
First-line zongertinib showed antitumor activity in treatment-naïve patients with advanced or metastatic HER2-mutant non-small cell lung cancer (NSCLC), providing a safe and effective oral targeted treatment alternative to chemotherapy, according to researchers at The University of Texas MD Anderson Cancer Center.
Results from the multi-site Phase Ia/Ib Beamion LUNG-1 trial, published today in The New England Journal of Medicine, reported a 76% objective response rate (ORR), indicating tumor shrinkage in 56 of 74 patients. Responses lasted for a median duration of 15.2 months, with no progression of disease for over 14 months.
This data supports the recent accelerated approval of zongertinib by the Food and Drug Administration (FDA) for the treatment of unresectable or metastatic HER2-mutant non-small cell lung cancer. The accelerated approval follows Breakthrough Therapy designation and prior FDA approval for previously treated patients in August 2025.
“We observed unprecedented response rates for this cancer subtype, and these findings led to zongertinib becoming the first FDA-approved treatment of its kind for these patients,” said principal investigator John Heymach, M.D., Ph.D., chair of Thoracic/Head and Neck Medical Oncology. “What’s particularly exciting is that just a few years ago, patients with this disease had no effective targeted therapies. Now, health care providers have a HER2-targeted treatment option that can make a meaningful difference.”
What is zongertinib and how can it benefit patients?
Lung cancer remains the leading cause of cancer-related death worldwide. Approximately 2-4% of patients with NSCLC have cancers driven by changes in the HER2 gene.
Zongertinib is an oral HER2 inhibitor that, unlike previous targeted therapies tested in this setting, selectively targets HER2 and spares the related EGFR protein. This means the drug can significantly reduce side effects while providing strong antitumor activity.
The study found that the most common side effects associated with zongertinib were diarrhea and rash with low instances of interstitial lung disease – a very serious complication associated with other treatments.
Was zongertinib effective in patients with brain metastases?
HER2-mutant NSCLC carries a high incidence of brain metastases. In this study, antitumor activity was observed across patient subgroups, regardless of specific HER2 mutation subtype or the presence of brain metastases.
The trial enrolled 74 patients between Nov. 2023 and Aug. 2025. Patients were treated with zongertinib (120 mg) at 53 sites globally. The median duration of treatment was 14 months, and treatment was ongoing in 46% of patients at data cutoff.
In the 30 patients with active brain metastases 47% had a confirmed objective response according to RANO-BM criteria. In the eight patients who received zongertinib in the first-line setting, four had an intracranial objective response or saw anti-tumor activity in the brain. Overall, median duration of intracranial response was 6.9 months, and median intracranial progression-free survival was 8.2 months
Limitations of this study included the open-label design and absence of a standard-of-care comparison arm. Further investigation is ongoing in a Phase III trial evaluating first-line zongertinib versus standard of care in patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous NSCLC.
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This study was funded by Boehringer Ingelheim. A full list of collaborating authors and their disclosures can be found in The New England Journal of Medicine.