This study evaluated BGB-16673, an investigational drug that degrades the BTK protein, in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), whose disease had transformed into a more aggressive form (Richter transformation) and who had tried several prior treatments. Among 24 patients, BGB-16673 was generally tolerable, with manageable side effects. Two-thirds of patients had grade ≥3 treatment-emergent adverse events (TEAEs). TEAEs of any grade that occurred in ≥15% of patients were decreased neutrophil count, nausea, diarrhea, peripheral edema, and pneumonia. One death occurred but was a result to the disease progressing, not due to treatment. About half responded to treatment, with some responses lasting more than six months. Responses were also observed in patients with high-risk genetic mutations. These results support further investigation of BGB-16673 in Richter transformation.

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