Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective T...

연구 요약

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 학술지에 발표된 이 연구는 Pereira H, Wölke S, Sadrolhefazi B 외 연구팀이 수행하였습니다.

이 연구는 '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.'에 대한 과학적 분석을 제공합니다.

핵심 내용

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-tz and 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-tz and Cmax were ∼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 tmax was 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.

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