Tacabrutideg (BGB-16673), a first-in-class oral BTK degrader, elicited a high overall response rates across dose levels in patients with relapsed/refractory
Across all dose levels (n = 67), the ORR was 85.1%, comprising 2 patients (3.0%) with a complete response (CR) or complete response with incomplete marrow recovery (CRi). At the recommended phase 2 dose (RP2D) of 200 mg (n = 17), the ORR was 94.1%, with 1 patient in CR/CRi (5.9%). Median time to first response at the RP2D was 2.8 months (range, 2.7-8.3), and median duration of response (DOR) was 20.6 months (range, 0.0-33.1); the median DOR across all doses was 20.7 months (range, 0.0-33.1) across all doses.
In August 2024,
CaDAnCe-101 is a phase 1, open-label, dose-escalation and -expansion study evaluating tacabrutideg monotherapy in adult patients with relapsed/refractory B-cell malignancies.
In the CLL/SLL cohorts, patients needed to meet 2018 International Working Group CLL criteria for treatment, and receipt of at least 2 prior therapies were required, including a covalent BTK inhibitor if approved for their disease. Adequate organ function and an ECOG performance status of 0 to 2 (0 to 1 in the European Union) were required.
Tacabrutideg was administered orally once daily in 28-day cycles across dose levels of 50 mg, 100 mg, 200 mg, 350 mg, and 500 mg.
The primary objectives of phase 1 were safety, tolerability, maximum tolerated dose, and determination of the RP2D, established at 200 mg once daily.
The median age among patients with CLL/SLL (n = 67) was 70 years (range, 47-91); 68.7% were male. Among patients with known mutation status, 25 of 66 (37.9%) harbored a BTK mutation at baseline.
In the CLL/SLL cohort, patients had received a median of 4 prior lines of therapy (range, 2-10); 94.0% had received a covalent BTK inhibitor, 82.1% had received a BCL-2 inhibitor, and 37 of 41 evaluable patients (90.2%) were refractory to their last covalent BTK inhibitor and last BCL-2 inhibitor. High-risk disease features were common at baseline; 65.7% harbored 17p deletions and/or TP53 mutations, 76.8% had unmutated IGHV, and 53.5% had complex karyotype with at least 3 chromosomal abnormalities.
Data presented reflected a cutoff of February 25, 2026. Median study follow-up was 25.4 months (range, 0.3-40.1).
Subgroup data showed that among patients refractory to their last covalent BTK inhibitor and last BCL-2 inhibitor (n = 37), the ORR was 83.8%. Among those who had received a prior covalent BTK inhibitor and BCL-2 inhibitor without a noncovalent BTK inhibitor (n=43), the ORR was 93.0%, and the ORR was 75.0% in those who had received all three classes (prior covalent BTK inhibitor, noncovalent BTK inhibitor, and BCL-2 inhibitor; n=12).
Patients with 5 or more prior lines of therapy (n = 29) achieved an ORR of 86.2%. Among those with 17p deletion and/or TP53 mutation (n = 44), the ORR was 79.5%; those with BTK mutations (n = 25) responded at a rate of 76.0%; and those with PLCG2 mutations (n = 10) responded at a rate of 90.0%. Responses were observed across all assessed BTK mutation subtypes, including the common C481S resistance mutation (ORR, 82%; n = 17).
The 24-month progression-free survival (PFS) rate was 53.8% (95% CI, 38.8%-66.6%), with a median PFS of 24.4 months (range, 0-35.9+) across the CLL/SLL cohort.
In a separate BTK inhibitor–naive expansion cohort (part 1f), 54 patients were enrolled across B-cell malignancies, including 29 with CLL/SLL (11 treatment-naive) as of a December 15, 2025, cutoff. Among CLL/SLL patients evaluable for efficacy (n = 22), the ORR was 86.4%, and no PFS events had occurred at 6 months.
Among the 67 patients with CLL/SLL treated at a median duration of exposure of 18.2 months (range, 0.2-36.4), 97.0% experienced at least one treatment-emergent adverse effect (TEAE) of any grade, and 62.7% had a grade 3 or higher TEAEs. Treatment-related grade 3 or higher TEAEs occurred in 34.3% of patients. Twelve patients (17.9%) discontinued treatment due to any TEAE, and 4 (6.0%) discontinued due to a treatment-related TEAE. No treatment-related deaths were reported.
The most common TEAEs of any grade occurring in at least 10% of patients included fatigue, contusion (bruising), diarrhea, neutropenia, anemia, pneumonia, cough, thrombocytopenia, COVID-19, dyspnea, peripheral edema, and pyrexia.
In patients who responded to treatment and had baseline cytopenias, rapid and sustained improvements were observed. Among patients with baseline thrombocytopenia (n = 22), median platelet count increased from 62.5 × 10⁹/L at baseline to 133.5 × 10⁹/L at week 9. Neutrophil counts and hemoglobin levels also improved in parallel with treatment response.
