The U.S. Food and Drug Administration has granted Priority Review to Boehringer Ingelheim's zongertinib (BI 1810631), potentially marking a significant advancement in the treatment of HER2-mutant advanced non-small cell lung cancer (NSCLC). The investigational therapy could become the first orally administered targeted treatment for this patient population who have received prior systemic therapy.
Strong Clinical Evidence Drives Priority Review
The FDA's decision was based on compelling data from the Phase Ib Beamion LUNG-1 trial's Cohort 1, which included 75 previously treated patients. The study demonstrated an objective response rate of 71%, with six-month progression-free survival and duration of response rates of 69% and 73%, respectively, in patients with mutations in the HER2 tyrosine kinase domain.
Zongertinib's safety profile proved particularly noteworthy, with only 5% of patients requiring dose reductions and 3% discontinuing treatment. The most common treatment-related adverse events were mild, primarily consisting of diarrhea (51%) and rash (27%). Importantly, no treatment-related interstitial lung disease cases were reported, and only one patient experienced grade 3 or higher treatment-related adverse events.
Addressing a Critical Unmet Need
HER2 mutations occur in approximately 2-4% of NSCLC cases and are associated with poor outcomes and increased risk of brain metastases. The current five-year survival rate for patients with HER2-mutant advanced NSCLC is less than 30%, highlighting the urgent need for effective targeted therapies.
"We believe zongertinib has the potential to transform the care of previously treated patients with HER2-mutant advanced non-small cell lung cancer," said Shashank Deshpande, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim.
Mechanism and Development Status
Zongertinib functions as an irreversible tyrosine kinase inhibitor that selectively targets HER2 while sparing EGFR, potentially reducing associated toxicities. The drug has already received Breakthrough Therapy Designation and Fast Track Designation from the FDA, as well as Orphan Drug Designation in Japan.
The FDA's Priority Review status shortens the review timeline from the standard 10 months to six months, with a decision expected in the third quarter of 2025. This expedited review reflects the significant unmet medical need in this patient population.
Ongoing Research
A Phase III trial, Beamion LUNG-2, is currently enrolling patients to evaluate zongertinib against the standard of care in HER2-mutant NSCLC. Additional studies are exploring the drug's potential in other solid tumors with HER2 alterations.
"Early screening and biomarker testing for mutations provide critical information to guide targeted therapies in personalized medicine," noted Courtney Granville, Chief Scientific Officer at GO2 for Lung Cancer. "This filing acceptance represents a significant step toward offering another option for individuals with a HER2 diagnosis, bringing hope and direction to cancer patients."
