The objective of this analysis was to report updated safety and efficacy results from the phase 1 portion of the CaDAnCe‑101 study evaluating BGB‑16673, an investigational Bruton tyrosine kinase (BTK) degrader, in patients with relapsed or refractory Waldenström macroglobulinemia (WM).
CaDAnCe‑101 is an ongoing, open‑label, phase 1/2 study. Eligible patients had confirmed relapsed or refractory WM had received at least two prior therapies with an anti-CD20 antibody and a covalent BTK inhibitor, and had an ECOG performance status of 0–2. BGB‑16673 was administered orally once daily at multiple dose levels. The primary phase 1 objectives were safety and tolerability, determination of the maximum tolerated dose, and selection of the recommended dose for expansion. The secondary endpoints were overall response rate (ORR, defined as ≥minor response; IWWM‑11 consensus criteria) and major response rate (MRR, defined as ≥partial response).
As of the December 15, 2025 data cutoff, 43 patients with relapsed or refractory WM received BGB–16673 (100 mg, n=15; 200 mg, n=15; 350 mg, n=13). The median age was 72 years (range, 46–81), and patients had received a median of 3 prior lines of therapy (range, 2–11). Prior therapies included an anti–CD20 antibody (100%), a covalent BTK inhibitor (100%), chemotherapy (93.0%), a proteasome inhibitor (32.6%), a BCL2 inhibitor (23.3%), and noncovalent BTK inhibitor (16.3%). Most patients (83.7%) discontinued prior BTK inhibitor therapy due to progressive disease. At data cutoff, 26 patients (60.5%) remained on treatment; among the 17 patients who discontinued, the primary reason for discontinuation was progressive disease in 6 patients (35.3%). Median study follow–up was 14.3 months (range, 0.2-37.3).
Any–grade treatment–emergent adverse events (TEAE) were reported in 95.3% of patients, and grade ≥3 events occurred in 60.5%. The most common any–grade events occurring in ≥25% of patients were neutropenia/neutrophil count decreased (37.2%), diarrhea (30.2%), and contusion (27.9%). Grade ≥3 adverse events reported in ≥10% of patients included neutropenia/neutrophil count decreased (34.9%) and anemia (14.0%). Grade ≥3 infections occurred in 18.6% of patients. No cases of atrial fibrillation were reported. Febrile neutropenia and major hemorrhage (grade 3 hematemesis) each occurred in one patient (2.3%). TEAEs led to treatment discontinuation in 11.6% of patients and dose reduction in 7.0% of patients. As previously reported, 3 patients (7.0%) died due to TEAEs.
Among 42 response–evaluable patients, the ORR was 85.7%, and the MRR was 76.2%. Very good partial responses were reported in 31.0% of patients. Median time to first overall response was 1.0 month (range, 0.9-8.2), and median time to best overall response was 2.8 months (range, 1.0-12.2). Responses were observed in patients with high–risk features, including BTK mutations, and in 82.9% of patients who had discontinued prior BTK inhibitor therapy due to progressive disease. After a progression–free survival (PFS) median follow–up of 16.6 months (95% CI, 13.8-19.5), the estimated 15–month PFS rate was 70.4% (95% CI, 52.6%-82.5%).
