Emerging HER2-Targeted Therapy Shows Promise in Treating Previously Managed Lung Cancers

Recent advancements in targeted cancer therapies have opened new avenues for treating non-small cell lung cancers (NSCLC) that harbor HER2 mutations. The HER2 inhibitor zongertinib has demonstrated significant clinical benefits for patients who have previously undergone treatment, especially those with specific HER2 mutations. According to the Phase Ia/Ib Beamion LUNG-1 trial, conducted by researchers from The University of Texas MD Anderson Cancer Center, patients treated with zongertinib experienced notable tumor response rates alongside manageable side effects.

Updated data presented at the AACR Annual Meeting 2025 by lead investigator Dr. John Heymach highlighted a median duration of response of 14.1 months and progression-free survival of 12.4 months. Notably, the trial previously reported an objective response rate of 71%, indicating substantial tumor shrinkage among 75 patients in the initial cohort. This response rate is considered unprecedented in this subtype of lung cancer. Dr. Heymach emphasized that the oral once-daily administration of zongertinib, combined with its improved safety profile over less selective inhibitors, makes it a promising option for patients in need of new treatments.

Unlike other tyrosine kinase inhibitors, zongertinib selectively targets HER2 while sparing EGFR, significantly reducing adverse effects such as diarrhea and rash. In the trial, grade three or higher side effects occurred in 17% of patients, predominantly diarrhea and rash, with no cases of interstitial lung disease reported. The study included three cohorts: patients with specific tyrosine kinase domain (TKD) HER2 mutations, those with non-TKD HER2 mutations, and patients previously treated with HER2-directed therapies like T-DXd. The data suggest that resistance to prior treatments does not necessarily confer cross-resistance to zongertinib, offering hope for patients with resistant or relapsed disease.

Regulatory agencies have granted zongertinib breakthrough therapy designation and priority review, reflecting its potential as an effective treatment option. Ongoing trials, such as the Beamion LUNG-2, are exploring zongertinib as a first-line therapy, and further studies are planned to evaluate its combination with other treatments and in different tumor types. These developments represent a significant step forward in managing HER2-mutant lung cancers.

This promising progress was published in the New England Journal of Medicine, providing a comprehensive view of the potential impact of zongertinib on future lung cancer therapies.

Source: https://medicalxpress.com/news/2025-04-her2-therapy-previously-lung-cancers.html