BTK Degrader BGB-16673 Effective for CLL in Phase I Trial

BGB-16673, an oral small molecule Bruton’s tyrosine kinase (BTK) degrader, showed promising activity in pretreated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to phase I data.

Ricardo Parrondo, MD, of the Mayo Clinic, presented updated preliminary data from the first-in-human phase I study on BGB-16673 at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.

Eligible patients had relapsed or refractory CLL or SLL with two or more prior therapies, an Eastern Cooperative Oncology Group performance status from zero to two, and adequate end-organ function. The primary goals of the study were to evaluate safety and tolerability and identify a recommended phase II dose.

As of November 2023, the analysis included 39 patients who received BGB-16673 at doses of 50 mg (n=1), 100 mg (n=5), 200 mg (n=15), 350 mg (n=14), or 500 mg (n=4).

CLL Treatment Outcomes With BGB-16673

In these patients, the median number of prior therapies was four (range, 2-8 therapies), including covalent BTK inhibitors (BTKi) in 95%, BCL2 inhibitors in 87%, and noncovalent BTKi in 26%. Among evaluable patients, 20 of 37 (54%) had del(17p) or TP53 mutations, 27 of 31 (87%) had unmutated IGHV, and 12 of 28 (43%) had three or more karyotypic anomalies.

The median follow-up was 3.3 months (range, 0.1-16.7 months). One dose-limiting toxicity occurred at 200 mg, though a maximum tolerated dose was not reached. The most common treatment-emergent adverse events were contusion, fatigue, diarrhea, and neutropenia.

Among 24 patients evaluable for response, the overall response rate was 67%, and the authors noted all responses but one were ongoing at the time of the presentation. Responses were achieved in patients treated at the lowest dose, with prior covalent BTKi (n=16) and noncovalent BTKi (n=22) therapy, and regardless of BTK mutation status, the report added.

“Emerging data from this ongoing, first-in-human study of the novel BTK degrader BGB-16673 demonstrate a tolerable safety profile and antitumor activity in heavily pretreated patients with CLL/SLL, including those with BTKi-resistant mutations,” Dr. Parrondo and colleagues summarized.

Reference

Parrondo R, Thompson M, Frustaci AM, et al. Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) CLL/SLL: results from the phase 1 BGB-16673-101 study. Abstract #S157. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.