New Oral Drug Shows Promise for Patients with HER2-Mutated Lung Cancer
A new oral drug called zongertinib helped many patients with advanced non-small cell lung cancer (NSCLC) whose tumors had a mutation in the HER2 gene, according to results from the Beamion LUNG-1 clinical trial. The findings were presented at the American Association for Cancer Research Annual Meeting.
The oral HER2 inhibitor zongertinib benefited patients with previously treated, HER2-mutated non-small cell #LungCancer in a phase I clinical trial, according to results presented by John V. Heymach, MD, PhD: https://t.co/mAZESpyQmF #AACR25 @MDAndersonNews pic.twitter.com/Ty6QqTlmVi
— AACR (@AACR) April 28, 2025
HER2 mutations are found in about 2% to 4% of NSCLC tumors. Right now, the only approved treatment that targets HER2 in lung cancer is an intravenous drug called trastuzumab deruxtecan. However, not all patients respond to the drug and it can cause serious side effects like lung damage, according to the presenting authors from The University of Texas MD Anderson Cancer Center.
Zongertinib is different from older HER2 drugs because it is more selective, meaning it focuses only on HER2 and avoids unwanted side effects linked to other targets. Early lab studies showed it might work better and be safer.
Andreas Saltos, MD
“HER2 is one of several cancer-associated genes that can be mutated in NSCLC, with other such genes including EGFR or ALK,” said Andreas Saltos, MD, a medical oncologist in the Thoracic Oncology Department at Moffitt Cancer Center. “For patients who have NSCLC that carries a HER2 mutation, there currently is no approved oral targeted therapy option like what we have for patients with EGFR or ALK-driven lung cancers.”
In the trial, 75 patients with specific HER2 mutations received 120 milligrams of zongertinib once daily. Among them, 71% saw their tumors shrink, and 96% had their cancer under control. The median length of tumor response was 14.1 months and the median time before cancer worsened was 12.4 months.
Researchers also studied other groups. Thirty percent of patients with less common HER2 mutations responded to the treatment, and 48% of patients who had already tried other HER2 drugs responded.
Zongertinib had fewer serious side effects than other treatments. Only 17% of patients in the main group had serious side effects and there were no reports of lung inflammation. Common side effects like rash and diarrhea were also rare.
“These updated results continue to show great promise for zongertinib as an oral targeted therapy option for patients with HER2-mutated NSCLC,” Saltos said. “This adds to the emerging data in multiple studies that we are approaching at an exciting future where we will have effective oral treatment options for advanced HER2-mutated NSCLC that might lead to better outcomes and also better quality of life”
The U.S. Food and Drug Administration is currently reviewing zongertinib for fast track approval. If approved, it would become the first oral targeted treatment available for patients with HER2-mutated NSCLC.
