The objective of this analysis was to report updated 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 relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
CaDAnCe‑101 is an ongoing, open‑label, phase 1/2 study. Eligible patients had relapsed or refractory CLL/SLL, had received ≥2 prior therapies, and had an ECOG performance status of 0–2 (0–1 in the EU). BGB‑16673 was administered orally once daily across multiple dose levels (50–500 mg). The primary phase 1 objectives were to assess safety and tolerability and to establish the maximum tolerated dose and recommended expansion dose. Secondary objectives included overall response rate (ORR) assessed per iwCLL 2018 criteria with partial response with lymphocytosis (PR-L) modification and Lugano 2014 criteria for SLL.
As of the December 15, 2025 data cutoff, 67 patients with relapsed or refractory CLL/SLL were treated (50 mg, n=1; 100 mg, n=22; 200 mg, n=17; 350 mg, n=15; 500 mg, n=12). The median age was 70 years (range, 47–91), and patients had received a median of 4 prior lines of therapy (range, 2–10). Prior therapies included covalent BTK inhibitors in 94.0% of patients, noncovalent BTK inhibitors in 20.9%, and BCL2 inhibitors in 82.1%. Median study follow‑up was 24.1 months (range, 0.3-37.7), and 52.2% of patients remained on treatment at data cutoff.
Any‑grade treatment‑emergent adverse events (TEAE) were reported in 97.0% of patients, and grade ≥3 events occurred in 61.2%. The most common any‑grade events (≥25%) were fatigue (37.3%), contusion (32.8%), diarrhea (29.9%), and neutropenia/neutrophil count decreased (29.9%). Grade ≥3 events that occurred in ≥5% of patients included infections (34.3%), neutropenia/neutrophil count decreased (25.4%), and thrombocytopenia/platelet count decreased (7.5%). TEAEs led to dose reduction in 13.4% and treatment discontinuation in 17.9% of patients, 4 (6.0%) of whom had treatment-related TEAEs (subdural hemorrhage, peripheral swelling and ecchymosis, maculopapular rash, and disseminated aspergillosis). Five deaths (7.5%), all due to infection, were reported, including one in the context of progressive disease.
Among all 67 treated patients, the ORR (≥ PR-L) was 85.1%. The rate of PR or better was 77.6%, and complete response/complete response with incomplete marrow recovery was reported in 3.0%. Median time to first response was 2.8 months (range, 2.0–19.4), and median duration of response was 20.7 months (range, 0–27.6). At the 200‑mg dose level, the ORR was 94.1% (16/17), including one complete response. The 18‑month progression‑free survival rate was 65.2% (95% CI, 50.9%-76.2%), with 31.3% experiencing progressive disease.
