Updated efficacy and safety results of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed/refractory Waldenström macroglobulinemia from the ongoing phase 1 CaDAnCe-101 study

作者：Constantine S. Tam, Chan Y. Cheah, John F. Seymour, Ricardo Parrondo, Mazyar Shadman, Damien Roos‐Weil, Stephan Stilgenbauer, Barbara Eichhorst, Herbert Eradat, Steven P. Treon, Yanan Zhang, Linlin Xu, Kunthel By, Shannon Fabre, Motohisa Takai, Amit Agarwal, Anna Maria Frustaci · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3583 · 被引用次数：1 · 研究领域：Chronic Lymphocytic Leukemia Research、Ubiquitin and proteasome pathways、Protein Degradation and Inhibitors

Abstract Introduction: BGB-16673 is an orally available protein degrader that blocks BTK signaling by tagging BTK for degradation through the cell's proteasome pathway, leading to tumor regression. CaDAnCe-101 (BGB-16673-101; NCT05006716) is an ongoing open-label, phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies. Here, updated safety and efficacy results of BGB-16673 are presented in patients with WM in the phase 1 portion of the study. Methods Eligible patients had confirmed relapsed/refractory (R/R) WM (≥2 prior therapies), an ECOG performance status of 0-2 (0-1 in the EU), and previous treatment with an anti-CD20 antibody and, in the US, Japan, and EU, a covalent BTK inhibitor. BGB-16673 was dosed once daily orally. The primary objectives of this phase 1 study were to evaluate safety and tolerability (NCI-CTCAE v5.0) and establish the maximum tolerated dose and recommended dose for expansion. A secondary objective was to evaluate the overall response rate (ORR; modified IWWM-6 consensus criteria), with the first assessment after 4 weeks of treatment. Results As of May 23, 2025, 42 patients with WM were enrolled and treated (100 mg, n=15; 200 mg, n=14; 350 mg, n=13). Median age was 72.0 years (range, 46-81 years), and the median number of prior therapies was 3 (range, 2-11), including prior covalent BTK inhibitors (n=42 [100%]), BCL2 inhibitors (n=10 [23.8%]), noncovalent BTK inhibitors (n=7 [16.7%]), anti-CD20 monoclonal antibodies (n=4...