Exploring a Novel BTK Degrader and Current Options for CLL

Justin Taylor, MD, assistant professor of medicine at the University of Miami, Sylvester Comprehensive Cancer Center, discusses the treatment landscape for chronic lymphocytic leukemia (CLL), and background on his early research assessing NX-2127 for this patient population.

NX-2127 is a Bruton's tyrosine kinase (BTK) degrader being evaluated for the treatment of patients with CLL. Taylor previously presented findings from NX-2127-001 (NCT04830137) a first-in-human, multicenter, open-label, phase 1 dose-escalation and cohort-expansion trial evaluating the safety, tolerability, and preliminary efficacy of NX-2127 for the treatment of adult patients with relapsed/refractory CLL and B-cell malignancies. A total of 28 patients were enrolled, including 17 with CLL or small lymphocytic lymphoma, at dose levels 100, 200 and 300 mg.

In addition to this BTK degrader, Taylor notes that patients with CLL have a variety of treatment options, and many agents are in clinical development. Some of these therapies include ibrutinib (Imbruvica), acalabrutinib (Calquence), zanubrutinib (Brukinsa), pirtobrutinib (Jaypirca), and venetoclax (Venclexta), and others are under evaluation in clinical trials.

Transcription:

0:10 | Earlier this year, we published some resistance mutations that we're seeing to noncovalent and some covalent BTK inhibitors. These results are looking at BTK degraders to overcome those resistance mutations for CLL.

0:27 | The good thing about CLL is that there are a lot of treatment options. The first-line treatments can differ based on patient's preferences and physicians’ comfort with the drugs. BTK inhibitors are a common frontline treatment. We now have ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, and others still in clinical trials. They're not frontline options, but they may be in the future. The other main frontline option is venetoclax, a BCL2 inhibitor that can be given in combination with the CD20 antibody. Venetoclax is a time-limited therapy, whereas ibrutinib or other BTK inhibitors are continuous therapy. I think it becomes more of a discussion with the patients as to which option they might prefer.