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ASH 2025 | The potential of BTK degraders in Waldenström’s: update from the CaDAnCe-101 trial of BGB-16673

Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA, Alfred Hospital and Monash University, Melbourne, Australia, provides an update on BGB-16673, a BTK degrader, in patients with Waldenström’s macroglobulinemia (WM) from the ongoing CaDAnCe-101 study (NCT05006716). Prof. Tam notes the encouraging results with this agent thus far, highlighting the promise of BTK degraders in patients with WM who have exhausted all available treatment options. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.

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Transcript

BGB-16673 is a BTK degrader. It’s able to overcome the traditional mutations associated with BTK, covalent and non-covalent BTK inhibitors. And in the first-in-human study, we also treated patients with Waldenström’s. So we reported the results of those patients. So 42 patients were treated. They were all, they’ve had a median of three lines of therapy and they’ve all had chemotherapy and they’ve all had BTK inhibitors in the past, so in a normal world those patients have got no further available lines of treatment...

BGB-16673 is a BTK degrader. It’s able to overcome the traditional mutations associated with BTK, covalent and non-covalent BTK inhibitors. And in the first-in-human study, we also treated patients with Waldenström’s. So we reported the results of those patients. So 42 patients were treated. They were all, they’ve had a median of three lines of therapy and they’ve all had chemotherapy and they’ve all had BTK inhibitors in the past, so in a normal world those patients have got no further available lines of treatment. 

On the BTK degrader study, those patients actually had a really good response, so we had an overall response rate of 85% and almost 30% of those patients actually got into a VGPR state, so VGPR means a 90% reduction in the paraprotein and our VGPR rate is actually 29%. So very impressive results in a highly refractory population of patients. So far, with about one year follow-up, the one-year progression-free survival is 78%. So it looks like the drug is well-tolerated, it’s effective, and it gives moderately durable remission so far, and obviously we need further follow-up. But for Waldenström’s patients, it means now they have another chance of life. They’ve had chemotherapy, they’ve had BTK inhibitors, and now BTK degraders can actually further extend their responses.

 

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