The objective of this analysis was to report safety and efficacy results from phase 1 of the ongoing CaDAnCe‑101 (BGB‑16673‑101) study evaluating BGB‑16673, an investigational Bruton tyrosine kinase (BTK) degrader, as monotherapy in patients with B‑cell malignancies who were naïve to BTK inhibitors.

CaDAnCe‑101 is an ongoing, open‑label, phase 1/2 study of BGB-16673 monotherapy in patients with B-cell malignancies. Eligible patients had a confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or Richter transformation (RT); had not received prior BTK inhibitor therapy; and had an ECOG performance status of 0–2 (0–1 in the EU). BGB‑16673 was administered orally at 200 mg once daily. The primary endpoint was safety. Secondary endpoints included overall response rate (ORR), with the first response assessment after 12 weeks, or 4 weeks for WM.

As of December 15, 2025, 54 patients with B‑cell malignancies were enrolled and treated (CLL/SLL, n=29; MCL, n=8; MZL, n=10; WM, n=5; RT, n=2). The median age was 68 years (range, 42–81). Patients had received a median of 2 prior lines of therapy (range, 0–9). Median follow-up was 8.3 months (range, 0.4-12.8) and 43 patients (79.6%) remained on treatment at data cut-off.

Any‑grade treatment‑emergent adverse events occurred in 83.3% of patients, and grade ≥3 events occurred in 33.3%. The most common any‑grade events were contusion (bruising; 27.8%) and petechiae (18.5%). Grade ≥3 events reported in at least two patients included neutropenia or neutrophil count decreased (14.8%) and anemia, hypertension, lower respiratory tract infection, pneumonia, and thrombocytopenia (each 3.7%). No major hemorrhage, opportunistic infections, or febrile neutropenia were reported. Treatment discontinuation occurred in 2 patients (3.7%; metastatic neoplasm, n=1; back pain, n=1), and one death (1.9%) was reported; none were considered treatment related and all occurred in patients with CLL/SLL. In patients with CLL/SLL (n=29), the most common grade ≥3 TEAE was neutropenia/neutrophil count decreased (20.7%).

Efficacy was reported for patients with CLL/SLL only due to small sample sizes in other cohorts. Among 22 evaluable patients, the ORR was 86.4% (19/22), including partial responses (n=15) and partial responses with lymphocytosis (n=4), with a median follow‑up of 8.2 months. All responses were ongoing at the data cutoff (n=19). The median time to first response was 2.8 months (range, 2.7-5.6). Responses were observed in all 4 patients with known unmutated IGHV status and in 4 of 6 patients with known del(17p) and/or TP53 mutation. At 6 months, no progression‑free survival events were observed.