ASH 2024 | CaDAnCe-101 study: preliminary efficacy and safety of the BTK degrader BGB-16673 in R/R indolent NHL

The CaDAnCe-101 study is investigating, it’s an ongoing dose escalation study of BGB-16673, which is a BTK protein degrader. It’s BTK targeting, but rather than being a small molecule inhibitor, it’s got a bifunctional domain which causes degradation via polyubiquitination of BTK in an Ikaros and Aiolos independent manner. It degrades the target and retains activity in patients with BTK mutations. And that was demonstrated quite nicely in a series of presentations because there were abstracts at this meeting looking at CLL cohort, Waldenström macroglobulinemia cohort, and indolent lymphoma. And in all of them, we saw fairly similar, we saw fairly similar results in the sense that the degrader remains effective in patients with, primarily patients who have been previously treated with covalent BTK inhibitors, and in some cases, prior non-covalent and BCL2 inhibitors with pretty encouraging response rates and a side effect profile, which really feels consistent with what other BTK targeting agents have. So, you know, bruising and things like that, but nothing untoward or unexpected. So it looks particularly encouraging across those, any histologic subtypes in which BTK inhibitors are effective. And the most encouraging thing is that they appear to retain efficacy in both covalent and non-covalent BTK exposed patients. So exciting data for that. And again, there are ongoing Phase two studies in a variety of histologic subtypes, including CLL, mantle cell lymphoma, and so on, both alone and in combination with other agents such as sonrotoclax and zanubrutinib. So very interesting molecule.

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