FDA Grants Priority Review to Boehringer's Zongertinib for HER2-Mutant Lung Cancer

Boehringer Ingelheim recently revealed that the U.S. Food and Drug Administration (FDA) has awarded Priority Review to its new drug application for zongertinib (BI 1810631). This investigational drug is designed for treating adults with non-small cell lung cancer (NSCLC) who have unresectable or metastatic tumors harboring HER2 (ERBB2) mutations and have undergone prior systemic therapy. Priority Review status is reserved for drugs that promise considerable advancements in treating serious conditions, with decisions expected in six months, as opposed to the typical ten months. As such, the Prescription Drug User Fee Act (PDUFA) action date is anticipated in the third quarter of 2025.

The foundation for this application lies in the successful results of the Phase Ib Beamion LUNG-1 trial. This study, particularly Cohort 1, recorded a 71% objective response rate in 75 previously treated patients with advanced NSCLC. The trial also showed six-month progression-free survival and duration of response rates at 69% and 73%, respectively, indicating promising effectiveness of zongertinib in patients with HER2 tyrosine kinase domain mutations.

Zongertinib's safety profile displayed a low incidence of adverse effects, with dose reductions and treatment discontinuations observed in only 5% and 3% of patients, respectively. The most common treatment-related adverse events (TRAEs) were mild, with diarrhea and rash occurring in 51% and 27% of patients, respectively. Serious TRAEs were rare, with one patient experiencing grade 3 or higher events. Notably, no cases of treatment-related interstitial lung disease were reported.

Courtney Granville, Chief Scientific Officer at GO2 for Lung Cancer, emphasized the importance of personalized medicine in cancer treatment. She noted that early screening and biomarker testing for mutations are crucial for guiding targeted therapies, offering newfound hope for those diagnosed with HER2 (ERBB2) mutations. This drug filing represents a significant milestone in expanding treatment options for these patients.

Zongertinib has previously received both Breakthrough Therapy Designation and Fast Track Designation from the FDA. These designations are intended to accelerate the development and review of drugs that could potentially surpass existing treatments in effectiveness. Additionally, Japan’s Pharmaceuticals and Medical Devices Agency has recognized zongertinib with Orphan Drug Designation.

The Beamion clinical trial program encompasses the Beamion LUNG-1 trial, which is an open-label, Phase I dose-escalation study of zongertinib as a monotherapy for individuals with unresectable or metastatic solid tumors with HER2 alterations. Further evaluation is underway in the Beamion LUNG-2 Phase III study, where zongertinib is being compared against standard care in patients with advanced NSCLC harboring HER2 tyrosine kinase domain mutations.

Zongertinib, also known as BI 1810631, is an investigational drug that works as an irreversible tyrosine kinase inhibitor (TKI), selectively targeting HER2 while sparing EGFR, thus minimizing associated toxicities. The orally administered treatment is currently being tested for efficacy in HER2-mutant advanced NSCLC, with additional studies ongoing for solid tumors with HER2 alterations.

Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases, with a high unmet need for new treatments, particularly for patients with advanced stages linked to HER2 mutations. These mutations are linked to poor prognosis and increased brain metastases. They can lead to uncontrolled cell growth and tumor proliferation, highlighting the critical need for innovative treatments like zongertinib.