Lydia Scarfò, MD, is an assistant professor of internal medicine at the Università Vita-Salute San Raffaele; as well as a consultant hematologist at the Strategic Research Program on CLL

Dr Scarfò on the Future of BGB-16673 in Relapsed/Refractory CLL/SLL

“We hope that with additional evidence we can confirm the efficacy and safety of the mechanism of action [of BGB-16673]. [This includes] this specific compound, but also BTK degraders in general.”

Lydia Scarfò, MD, an assistant professor of internal medicine and a consultant hematologist for the Strategic Research Program on CLL at the Università Vita-Salute San Raffaele, discussed future research directions for the BTK degrader BGB-16673 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

2025 European Hematology Association Congress

, Scarfò presented data from the phase 1 CaDAnCe-101 trial (NCT05006716) which evaluated the safety and efficacy of BGB-16673 in patients with CLL/SLL who received at least 2 prior therapies. Among efficacy-evaluable patients (n = 66), the overall response rate (ORR) was 80.3%, including a complete remission (CR)/CR with incomplete count recovery rate of 3.0%. Notably, patients treated at the 200-mg dose level (n = 16) achieved an ORR of 93.8% with 1 CR. The median time to response was 2.8 months (range, 2.0-10.9).

Scarfò noted that considering the positive findings from CaDAnCe-101, multiple clinical trials are now underway comparing BGB-16673 with standard of care therapies for the treatment of patients with CLL/SLL. In the phase 3 CaDAnCe-302 trial (NCT06846671), BGB-16673 is being compared with investigator’s choice of treatment in patients with CLL/SLL who previously received a BTK inhibitor and a BCL2 inhibitor. In the phase 3 CaDAnCe-303 study (NCT06970743), BGB-16673 is being compared with investigator’s choice of therapy in patients with CLL/SLL who previously received a covalent BTK inhibitor.

Investigators hope that positive findings from these phase 3 studies will eventually lead to the integration of BGB-16673 into the therapeutic armamentarium of CLL/SLL, Scarfò said. Another goal of future study will be to confirm the safety and efficacy of the mechanism of action of BGB-16673 so that it and other BTK degraders can be used for the treatment of patients with CLL/SLL, Scarfò concluded.

Videos

Lydia Scarfò, MD, discusses future research directions for BGB-16673 in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.

Lydia Scarfò, MD, presented updated Phase 1 data from the CaDAnCe-101 study showing that BGB-16673, a novel BTK degrader, demonstrated a manageable safety profile and durable responses in heavily pretreated patients with R/R CLL/SLL, including those with prior BTKi exposure and high-risk mutations.

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

Lydia Scarfò, MD, presented updated phase 1 data from the CaDAnCe-101 study showing that BGB-16673, a novel BTK degrader, demonstrated a manageable safety profile and durable responses in heavily pretreated patients with R/R CLL/SLL, including those with prior BTKi exposure and high-risk mutations.

Lydia Scarfò, MD, explains the rationale for evaluating the BTK degrader BGB-16673 for patients with relapsed/refractory CLL.

Dr Scarfò on the Rationale for Evaluating BGB-16673 in Relapsed/Refractory CLL

“The treatment of patients with chronic lymphocytic leukemia has radically changed in the last few years, thanks to the introduction of BCL-2 and BTK inhibitors. [However,] the issue is that patients exposed to BTK inhibitors and BCL-2 inhibitors still have the chance to relapse, and they become a difficult-to-treat population.”

Lydia Scarfò, MD, an assistant professor of internal medicine at the Università Vita-Salute San Raffaele and a consultant hematologist at the Strategic Research Program on CLL, explained the rationale for evaluating the BTK degrader BGB-16673 for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Over the past few years, the treatment landscape of CLL has significantly changed, largely because of BCL-2 and BTK inhibitors, Scarfò began. Nevertheless, she noted that patients with CLL who are exposed to BTK and BCL2 inhibitors may still relapse, which can make this particular patient population more difficult to treat. Therefore, utilizing treatments with a different mechanism of action could help overcome resistance and help achieve long-term disease control, she explained.

BGB-16673 targets BTK, which is essential for the survival and proliferation of CLL cells. Unlike conventional BTK inhibitors, BGB-16673 targets BTK degradation through the proteasome pathway, Scarfò concluded.

The phase 1 CaDAnCe-101 trial (NCT05006716) evaluated the safety and efficacy of BGB-16673. Results from the study showed that, at the 200 mg dose level (n = 16), the overall response rate was 93.8%. This comprised 1 patient who achieved a complete response (CR) or CR without incomplete marrow recovery, and 12 patients who achieved partial responses.

The most common treatment-emergent adverse effects (TEAEs) were fatigue (37%), contusion (30%), diarrhea (29%), neutropenia (29%), anemia (23%), cough (18%), pyrexia (17%), pneumonia (16%), COVID-19 (15%), dyspnea (15%), increased lipase (15%), thrombocytopenia (14%), arthralgia (12%), peripheral edema (12%), increased amylase (11%), and nausea (11%). Of note, low-grade atrial fibrillation occurred in 2 patients, and major hemorrhage occurred in 2 patients, one being a grade 3 subdural hemorrhage.

Dr Scarfò on Updated Safety Data With BGB-16673 in Relapsed/Refractory CLL/SLL

Lydia Scarfò, MD, an assistant professor of internal medicine at the Università Vita-Salute San Raffaele; as well as a consultant hematologist at the Strategic Research Program on CLL, discussed updated safety and efficacy data from the ongoing phase 1 CADANCE-101 trial (NCT05006716) evaluating the BTK degrader BGB-16673 in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.

Lydia Scarfò, MD, discusses long-term data with BGB-16673 in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.

Lydia Scarfò, MD

Articles

Dr Scarfò on the Future of BGB-16673 in Relapsed/Refractory CLL/SLL

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

Dr Scarfò on the Rationale for Evaluating BGB-16673 in Relapsed/Refractory CLL

Dr Scarfò on Updated Safety Data With BGB-16673 in Relapsed/Refractory CLL/SLL