Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies

Pereira H, Wölke S, Sadrolhefazi B, Esmaeili H, Wind S, Gan G, Müller F, Minich D, Bader K, Grempler R, Law YK, Roessner PM (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Molecular Pharmaceutics American Chemical Society

Book Volume: 22

Pages Range: 6531-6538

Journal Issue: 11

DOI: 10.1021/acs.molpharmaceut.5c00832

Abstract

Human epidermal growth factor receptor 2 (HER2), also known as ErbB2, is mutated in various solid tumors. Zongertinib (BI 1810631) is a novel, orally administered, HER2-specific tyrosine kinase inhibitor that spares the epidermal growth factor receptor (EGFR), limiting EGFR-related adverse events. Zongertinib has recently received accelerated approval in the United States and China for patients with advanced, previously treated, HER2 mutant NSCLC. Two Phase I open-label crossover studies evaluated the effect of a high-fat, high-calorie meal on zongertinib bioavailability at two doses: 30 mg (NCT05380947) and 240 mg (NCT06075277). Healthy male participants were randomized to treatment sequences in which they received single doses of zongertinib (spray-dried dispersion formulations) under fed and fasted conditions. The washout interval was ≥14 days. The primary end points were the area under the concentration–time curve of zongertinib in plasma over the time from 0 to the last quantifiable data point (AUC0-tz), and the maximum measured concentration of zongertinib in plasma (Cmax). In NCT05380947, 13 participants received 30 mg of zongertinib. The ratios of adjusted geometric means demonstrated lower AUC0-tzand Cmax, under fed (n = 9) versus fasted (n = 12) conditions (fed/fasted, % [90% CI]: AUC0-tz, 74.2% [67.6–81.6]; Cmax, 53.5% [40.5–70.8]). In NCT06075277, the ratios of adjusted geometric means for AUC0-tzand Cmaxwere ∼26% higher under fed versus fasted conditions (fed/fasted, % [90% CI]: AUC0-tz, 126.6% [112.1–143.1]; Cmax, 126.1% [106.3–149.6]). In both studies, median tmaxwas delayed (NCT05380947/NCT06075277) under fed (3/4 h) versus fasted (1.5/2 h) conditions. Zongertinib demonstrated good bioavailability in healthy participants. A small dose-dependent food effect was observed.

Involved external institutions

hVIVO (United Kingdom) GB United Kingdom (GB) Boehringer Ingelheim Pharma GmbH & Co. KG DE Germany (DE) Staburo GmbH DE Germany (DE)

How to cite

APA:

Pereira, H., Wölke, S., Sadrolhefazi, B., Esmaeili, H., Wind, S., Gan, G.,... Roessner, P.M. (2025). Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies. Molecular Pharmaceutics, 22(11), 6531-6538. https://doi.org/10.1021/acs.molpharmaceut.5c00832

MLA:

Pereira, Hélène, et al. "Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies." Molecular Pharmaceutics 22.11 (2025): 6531-6538.

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