About zongertinib
Mechanism of action
Zongertinib selectively and covalently binds to the tyrosine kinase domain of mutated HER2 receptors.1 Selective binding blocks aberrant downstream signaling, while sparing wild-type EGFR signaling, thereby avoiding wild-type EGFR-associated toxicity.1
Pan-ErbB TKIs are impeded by WT EGFR associated toxicity. Improved selectivity of HER2 TKIs may result in better tolerability and potential for more effective dosing.2
Zongertinib mechanism of action1
EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; WT, wild type.
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As of September 29, 2023, 61 patients have been treated in Phase 1a of Beamion LUNG-1 and maximum tolerated dose has not been reached. Zongertinib was well tolerated with low rates of EGFR-mediated adverse events. Doses taken into optimization were 240 mg and 120 mg once a day.3
In Phase Ib of the trial, 42 patients with pre-treated NSCLC with a HER2 TKD mutation have been treated as of July 31, 2023. Sixty seven percent (66.7%) experienced treatment related adverse events, mostly grade 1 or 2. The most common treatment related adverse event was diarrhea (28.6%). There have been no treatment discontinuations due to adverse events. Objective response rate was 73.9% and disease control rate was 91.3%. The first interim analysis in this cohort passed and the trial is ongoing.3
Yamamoto N, et al. WCLC 2023. Abstract MA13.08.
Heymach J, et al. Clin Lung Cancer 2023;e65-e68.
Heymach J, et al. NACLC 2023. OA01.28.