BGB-16673 Demonstrates High Efficacy in Relapsed CLL/SLL Patients

In a significant advance in oncology, the investigational drug BGB-16673 has shown a promising safety profile and a remarkable overall response rate (ORR) of 84.8% in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This data emerged from the phase 1/2 CaDAnCe-101 trial, presented at the 2025 European Hematology Association Congress held in Milan, Italy, from June 12 to 15, 2025.

The study, led by Dr. Lydia Scarfò, a physician scientist at the B-cell Neoplasia Unit and assistant professor at the Università Vita-Salute San Raffaele in Milan, involved a cohort of 66 patients with a median follow-up of 15.6 months. The findings indicate that BGB-16673 is well tolerated, with treatment-emergent adverse events (TEAEs) reported in 95.5% of patients, primarily including fatigue (37%), contusion (30%), and diarrhea (27%). Notably, serious adverse events were less frequent and not directly related to the therapy, with only four patients experiencing TEAEs that led to death, none of which were attributed to the medication.

Dr. Scarfò emphasized the drug's significant antitumor activity across various high-risk subgroups, including patients with Bruton’s tyrosine kinase (BTK) mutations and those previously exposed to BTK and BCL2 inhibitors. The most encouraging results were seen at the 200 mg dosage level, which yielded a remarkable 93.8% ORR, demonstrating the drug's potential for further clinical development.

The trial aimed to assess the drug's safety and tolerability, with secondary endpoints focused on pharmacokinetics and preliminary antitumor activity. Patients enrolled had undergone at least two prior therapies and displayed high-risk features such as unmutated immunoglobulin heavy chain variable region (IGHV) and 17p deletion.

BGB-16673 operates as a novel oral protein degrader, strategically designed to inhibit BTK signaling by tagging the protein for degradation via the proteasome pathway. This mechanism allows for tumor regression, making it a promising candidate in the ongoing battle against CLL and SLL, particularly in those with treatment-resistant disease.

According to Dr. Scarfò, the drug's ability to elicit responses regardless of prior treatment history or specific genetic mutations highlights its potential as a transformative therapy for patients facing limited options. The ongoing phase 2 and 3 trials will further evaluate BGB-16673's efficacy and safety, with the oncology community closely monitoring its progress.

In conclusion, the emergence of BGB-16673 marks a hopeful development in the treatment landscape for relapsed/refractory CLL/SLL, with its high ORR and manageable safety profile potentially paving the way for new therapeutic avenues in hematologic malignancies. Experts anticipate that these findings may lead to future regulatory approvals, offering renewed hope to patients challenged by these aggressive cancers.