This application is based on positive data from the Phase 1b clinical trial Beamion LUNG-1. Data from Patient Cohort 1 (N=75) showed that among patients carrying HER2 tyrosine kinase domain mutations, the objective response rate (ORR) reached 71%, with a six-month progression free survival rate and response duration rate of 69% and 73%, respectively.
The results previously announced at the 2024 ESMO Asia Annual Meeting of the European Society of Oncology showed that as of August 29, 2024, the disease control rate (DCR) of zongertinib reached 93%, and 55% of patients who achieved remission were still receiving treatment.
In addition, data presented at the 2024 World Lung Cancer Congress also showed that zongerinib has preliminary brain activity. According to the blind independent central review (BICR) assessment, 33% (120 mg, n=27) and 40% (240 mg, n=25) of asymptomatic brain metastasis patients achieved confirmed objective remission, with disease control rates of 74% and 92%, respectively. NSCLC tumors often metastasize to the central nervous system, which is associated with poor prognosis and quality of life for patients. Up to 30% of NSCLC patients diagnosed with HER2 mutations experience brain metastases.
In terms of safety, the dose reduction and treatment termination rates of zongerinib are relatively low, at 5% and 3%, respectively. Most adverse events (TRAEs) associated with zongertinib are mild, with diarrhea and rash being the most common, with incidence rates of 51% and 27%, respectively. No new safety signals were observed. Among patients receiving zongertinib treatment, only one case developed grade 3 or above TRAEs, and no treatment-related interstitial lung disease (ILD) cases were reported.
Zongertinib is an oral, irreversible HER2 tyrosine kinase inhibitor. Due to the fact that the drug does not bind to wild-type EGFR, its toxicity is relatively low. Zongertinib was granted fast track status by the US FDA in 2023 and subsequently received breakthrough therapy recognition from both the US FDA and the China National Medical Products Administration's Center for Drug Evaluation (CDE) in 2024. It is used to treat adult patients with advanced NSCLC who have received systemic therapy and carry HER2 mutations. The Beamion LUNG-2 global phase 3 clinical trial is currently underway, aimed at evaluating the efficacy of zongertinib as a first-line therapy in advanced NSCLC patients carrying HER2 mutations compared to standard treatment.
<Reprinted from WuXi AppTec>
