Novel BTK Degrader Shows Activity in CLL/SLL Regardless of Mutation Status

In a conversation with CancerNetwork® at the European Hematology Association 2025 Congress, Lydia Scarfò, MD, spoke about the potential advantages that BGB-16673, an investigational Bruton tyrosine kinase (BTK) degrader, may offer compared with other treatment modalities in relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). She spoke in the context of findings from the phase 1/2 CaDAnCe-101 trial (NCT05006716) assessing the agent among patients with relapsed/refractory CLL/SLL that she presented at the congress.

According to Scarfò, a physician-scientist at the B-Cell Neoplasia Unit and an assistant professor at the Università Vita-Salute San Raffaele in Milan, Italy, BGB-16673 demonstrated a “reassuring” ability to target BTK for degradation in both wild-type and mutated proteins. Additionally, regarding potential subgroup benefits, she stated that no specific predictive factors of response were identified at the time of analysis. She noted that investigators continue to evaluate mutational statuses as patients continue to enroll in the trial.

Data from the CaDAnCe-101 trial showed that among 66 evaluable patients with CLL or SLL, BGB-16673 produced an overall response rate of 84.8%, which included partial responses in 66.7% and a complete response (CR) or CR with incomplete marrow recovery in 4.5%.

Transcript:

The greatest advantage of the BTK degrader could be related to the fact that it’s able to target BTK for degradation regardless of the mutation status, meaning that it’s targeting for degradation both in the wild-type protein [and] the mutated protein. And we know that at the time of progression with covalent BTK inhibitors, a relevant proportion of patients is carrying mutated BTK. It’s reassuring that the BTK degrader works in both mutated and wild-type BTK.

We didn’t identify any specific factor predictive of better or worse response. We are still analyzing the mutational status as the patients enroll [in] the trial. Of course, [it is important] to understand in those who progressed what the mechanism was behind the progression. But it’s too early to provide a patient profile who would benefit the most from the BTK degrader treatment.

Reference

Scarfò L, Parrondo RD, Thompson MC, et al. Updated efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients (pts) with relapsed or refractory (R/R) CLL/SLL: results from the ongoing phase (ph) 1 CADANCE-101 study. Abstract presented at: European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Abstract S158.