The novel BTK degrader BGB-16673 demonstrated significant antitumor activity and was generally well tolerated without unexpected toxicities for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to Lydia Scarfò, MD.
Data from the phase 1/2 CaDAnCe-101 trial (NCT05006716), presented at the 2025 European Hematology Association Congress, revealed that, at a median follow-up of 15.6 months (range, 0.3-30.6+), patients with relapsed/refractory CLL/SLL (n = 66), experienced any-grade treatment-related adverse effects (TEAEs) at a rate of 95.5%, of which 74.2% were treatment-related and 60.6% were grade 3 or greater.
Furthermore, patients treated at the 200-mg dose level of BGB-16673 achieved an overall response rate (ORR) of 93.8%, including 1 complete response, 12 partial responses, and 2 partial responses with lymphocytosis. The 12-month progression-free survival (PFS) rate was 77.4%. (95% CI, 63.1%-86.8%).
“We have made great progress in the past few years in the treatment of patients with CLL, but the disease remains incurable in the majority of patients, so we need to increase the therapeutic options available, and BTK degraders look very promising,” Scarfò said during an interview with OncLive® at the meeting.
In the interview, Scarfò discussed the rationale for CaDAnCe-101, the mechanism of action of BGB-16673, safety and efficacy data from the study, and future directions for the novel BTK degrader.
Scarfò is a physician scientist at the B-Cell Neoplasia Unit and an assistant professor at the Università Vita-Salute Raffaele in Milano, Italy.
OncLive: What was the rationale for CaDAnCe-101?
Scarfò: The treatment of patients with CLL has radically changed in the last few years, thanks to the introduction of BCL2 and BTK inhibitors. The issue is that patients exposed to BTK and BCL2 inhibitors still have a chance of relapse, and they become a very difficult-to-treat population, so we need drugs that act with a different mechanism of action to overcome resistance and achieve long-term disease control.
What is the mechanism of action of BGB-16673?
BGB-16673 is a BTK degrader, meaning that the target is BTK, which is crucial for the survival and proliferation of CLL cells. However, instead of inhibiting the enzymatic activity of BTK, BGB-16673 targets BTK for degradation via the proteasome pathway.
What were the key design characteristics of CaDAnCe-101?
The phase 1 study is a basket trial [that included] patients with different B-cell malignancies and were enrolled into the trial we recently presented. [At the EHA Congress,] we have presented the results of the use of BGB-16673 in patients with relapsed/refractory CLL, both in the dose escalation and in the dose expansion phase of the trial.
What were the updated safety findings presented at EHA?
The reassuring thing is that we can confirm that BGB-16673 is generally well tolerated, with no unexpected toxicities associated with the use of this drug because the target is BTK. We do expect some cardiovascular adverse effects and some bleeding events, but they were very limited in the patient cohort. We also have to take into consideration that the follow-up remains pretty short.
What were the key efficacy data?
We have evaluated the ORR in the whole patient population, and we are happy to confirm that BGB-16673 is effective in the majority of patients, and in particular, at the recommended dose for the expansion phase of 200 mg daily, the ORR is 93.8% and we now have longer follow-up. Therefore, we can confirm that in terms of PFS, the response is endurable with a 12-month PFS rate of 77.4%.
What are the next steps for this research?
Thanks to the results of this phase 1/2 trial, several trials are currently ongoing trying to compare BGB-16673 with the standard of care. Several phase 2 and phase 3 trials are currently being performed to understand how to add this [therapy] to our therapeutic armamentarium in [clinical practice].
We hope that with additional evidence, we can confirm the efficacy and the safety of these mechanisms of action, of the specific compound, but also in general, of the use of a BTK degrader as a potential mechanism of action. In the near future, we hope we can add these mechanisms of action to our therapeutic armamentarium.
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. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S158.