Relative Bioavailability, Food Effect, and Bioequivalence Studies to Assess a New Zanubrutinib 160‐mg Tablet: Results From 2 Phase 1 Studies in Healthy Volunteers

Zanubrutinib is a next‐generation Bruton tyrosine kinase inhibitor approved for treating B‐cell malignancies. Two phase 1 studies evaluated a new 160‐mg zanubrutinib tablet versus 80‐mg capsules. In study BGB‐3111‐115 (n = 43), a randomized 3‐period crossover trial, relative bioavailability and food effects were assessed. Under fasted conditions, systemic exposure (area under the concentration‐time curve [AUC]) was comparable between tablets and capsules at both 160‐ and 320‐mg doses. A high‐fat meal increased tablet maximum plasma concentration (C max ) by 47%‐79% but had minimal effect on AUC (<18%), supporting administration with or without food. Study BGB‐3111‐114 (n = 58) was a randomized, replicate crossover study that evaluated bioequivalence (BE) under fasted conditions. Geometric mean ratios of AUC 0‐t and AUC 0‐∞ (tablets vs capsules) were 1.00 (90% confidence interval [CI] 0.95‐1.05) and 0.99 (90% CI 0.94‐1.04), meeting BE criteria. Tablet C max was modestly higher (geometric mean ratio 1.22, 90% CI 1.14‐1.30), with no expected clinical impact based on established zanubrutinib exposure‐response relationships. Both formulations were well tolerated, with no serious adverse events. In vitro testing showed tablets readily dispersed into a stable suspension suitable for nasogastric tube administration. Together, these results supported zanubrutinib tablets as a flexible alternative to capsules, with the potential to reduce pill burden (4 capsules vs 2 tablets) and improve long‐term adherence.