Zongertinib Receives FDA Priority Review in HER2–Mutant Advanced NSCLC

Efficacy results from cohort 1 of the phase 1b Beamion LUNG-1 trial support the decision to review zongertinib in HER2-mutant advanced NSCLC.

The FDA granted priority review to a new drug application for zongertinib (BI 1810631) as a treatment for adult patients with unresectable or metastatic HER2-mutant non–small cell lung cancer (NSCLC) who have received prior systemic therapy, according to a news release from the drug’s developers, Boehringer Ingelheim.¹

The agency has set a Prescription Drug User Fee Act date in the third quarter of 2025 for zongertinib in this patient population.

Supporting the decision were data from cohort 1 of the phase 1b Beamion LUNG-1 trial (NCT04886804) assessing zongertinib in patients with HER2–positive advanced or metastatic NSCLC. According to the cohort 1 (n = 75) findings, the objective response rate (ORR) in this patient population was 71%. Additionally, the 6-month progression-free survival (PFS) and duration of response (DOR) rates were 69% and 73%, respectively.

“Personalized medicine has revolutionized cancer treatment,” Courtney Granville, PhD, MSPH, chief scientific officer of GO2 for Lung Cancer, said in the news release.¹ “Early screening and biomarker testing for mutations provide critical information to guide targeted therapies in personalized medicine. This filing acceptance represents a significant step toward offering another option for individuals with a HER2 diagnosis, bringing hope and direction to [patients with] cancer.”

Patients with HER2–mutant NSCLC in the phase 1b Beamion LUNG-1 study were assigned to receive 120 mg of oral zongertinib once or twice daily.² Patients were initially treated in a dose-escalation portion of the trial, and once the highest tolerated dose of zongertinib was found, they were treated in a dose-expansion cohort. Those treated remained on trial for as long as they received benefit from and tolerated the agent.

According to data presented at the IASLC 2024 World Conference on Lung Cancer (WCLC), patients in cohort 1 of the phase 1b trial had a median age of 62 years (range, 30-80), and most patients were female (68%).³ Furthermore, 53% of patients were Asian, 56% received 1 prior line of systemic therapy, and 63% had an ECOG performance status of 1. Notably, 37% of patients in this cohort had brain metastases.

The primary end point of the first cohort of the phase 1b trial was ORR as assessed by central independent review (CIR). Secondary end points included disease control rate, PFS, ORR according to response assessment in neuro-oncology for brain metastases as assessed by CIR for those with central nervous system lesions, DOR, dose-limiting toxicities, and safety.

Zongertinib was well tolerated, with most treatment-related adverse events (TRAEs) considered mild in severity and no new safety signals observed. The most common any-grade TRAEs were diarrhea (51%) and rash (27%). Grade 3 or higher TRAEs occurred in 1 patient, and no interstitial lung disease cases were observed.

Treatment with zongertinib resulted in 5% of patients experiencing dose reductions. Additionally, 3% of patients experienced dose discontinuations.

Zongertinib was previously granted breakthrough therapy designation and fast track designation by the FDA for adult patients with pretreated HER2-mutant advanced, unresectable, or metastatic NSCLC. Additionally, Japan’s Pharmaceuticals and Medical Devices Agency recently granted orphan drug designation to zongertinib, according to the news release.

“We believe zongertinib has the potential to transform the care of previously treated patients with HER2-mutant advanced [NSCLC] and are hopeful about the continued research in other tumor types and lines of therapy,” Shashank Deshpande, member of the Board of Managing Directors and head of Human Pharma at Boehringer Ingelheim, said in the news release.¹ “Priority review illustrates the urgent need in this patient population and the possibility for zongertinib to be a groundbreaking innovation for patients with limited treatment options.”

References

1. Boehringer’s zongertinib receives priority review from U.S. FDA for the treatment of HER2 (ERBB2)-mutant advanced non-small cell lung cancer. News release. Boehringer Ingelheim. February 19, 2025. Accessed February 19, 2025. https://tinyurl.com/4475t495
2. Beamion LUNG-1: a study to test different doses of zongertinib in people with different types of advanced cancer (solid tumours with changes in the HER2 gene). ClinicalTrials.gov. Updated February 10, 2025. Accessed February 19, 2025. https://tinyurl.com/3w9y6hb6
3. Ruiter G, Tu H-Y, Ahn M-J, et al. Phase 1b analysis of Beamion LUNG-1: zongertinib (BI 1810631) in patients with HER2-mutant NSCLC. J Thorac Oncol. 2024;19(suppl 10):S4-S5. doi:10.1016/j.jtho.2024.09.018