HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors
John V Heymach1, Frans Opdam2, Minal Barve3
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
Purpose:
Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors.
Materials And Methods:
Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); tumor response was a secondary end point.
Results:
As of May 23, 2024, 105 patients were treated. Two DLTs occurred during the MTD evaluation period; MTD was not reached (NR). The recommended doses for expansion were 120 mg once daily and 240 mg once daily. Treatment-related adverse events (TRAEs; any/grade ≥3) occurred in 82%/10% of patients. The most common TRAEs (any/grade ≥3) included diarrhea (50%/1%), rash (16%/2%), anemia (10%/0%), decreased appetite (10%/1%), and increased alanine transaminase (10%/4%). The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response was 12.7 months (95% CI, 6.9 to NR). In 54 patients with NSCLC, confirmed ORR was 35% (95% CI, 24 to 49). Activity was observed in patients with A775_G776insYVMA (ORR, 38%) and those who had received previous HER2-directed therapy (ORR, 28%). In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR).
Conclusion:
Zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with HER2-altered tumors, including those with HER2-mutant NSCLC.
Insights
Zongertinib shows promise in treating HER2-altered cancers, including non-small cell lung cancer (NSCLC). The novel tyrosine kinase inhibitor demonstrated antitumor activity with a manageable safety profile in a Phase Ia/Ib trial.
Area of Science:
- Oncology
- Medical Research
Background:
- Human epidermal growth factor receptor 2 (HER2) alterations are present in various solid tumors.
- Non-small cell lung cancer (NSCLC) is one such malignancy where HER2 alterations can be found.
- Targeted therapies are crucial for treating cancers with specific genetic alterations.
Purpose of the Study:
- To assess the safety and efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor.
- To evaluate zongertinib in patients with HER2-altered solid tumors, including NSCLC.
- To determine the maximum tolerated dose (MTD) and recommended doses for expansion in the Beamion LUNG-1 trial.
Main Methods:
- The Beamion LUNG-1 trial is a multicenter, multicohort Phase Ia/Ib study.
- Zongertinib was administered at various doses (15-150 mg twice daily, 60-360 mg once daily).
- Primary endpoints included MTD and dose-limiting toxicities (DLTs); tumor response was a secondary endpoint.
Main Results:
- 105 patients were treated; MTD was not reached. Recommended doses for expansion were 120 mg and 240 mg once daily.
- Treatment-related adverse events (TRAEs) occurred in 82% of patients, with diarrhea and rash being most common.
- Overall response rate (ORR) was 30% across all tumors and 35% in NSCLC patients. In NSCLC, median progression-free survival was 17.2 months with once-daily dosing.
Conclusions:
- Zongertinib exhibits a manageable safety profile.
- Preliminary antitumor activity was observed in patients with HER2-altered tumors.
- Zongertinib shows potential for treating HER2-mutant NSCLC.
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