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IMS 2024 | First-in-human results of the anti-BCMA antibody-drug conjugate HDP-101 in R/R myeloma
Marc Raab, MD, German Cancer Research Center, Heidelberg, Germany, discusses the first-in-human results of HDP-101, an anti-BCMA antibody-drug conjugate (ADC) for relapsed/refractory multiple myeloma (R/R MM). Dr Raab explains the mechanism of action of this novel agent, which targets both proliferative and resting cells, and has shown responses in heavily pre-treated patients. This interview took place at the 21st International Myeloma Society (IMS) Annual Meeting, held in Rio de Janeiro, Brazil.
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Transcript
The anti-BCMA drug conjugate HDP-101 is an antibody-drug conjugate targeting BCMA but with a different payload. It’s an alpha-amanitin derivative which is actually known as a poison from a mushroom, which usually of course would be not a good idea as a drug. However, it has some great advantages. So if you really bring it into specific cells, that’s why it’s coupled to an antibody, right? Targeting BCMA and myeloma cells...
The anti-BCMA drug conjugate HDP-101 is an antibody-drug conjugate targeting BCMA but with a different payload. It’s an alpha-amanitin derivative which is actually known as a poison from a mushroom, which usually of course would be not a good idea as a drug. However, it has some great advantages. So if you really bring it into specific cells, that’s why it’s coupled to an antibody, right? Targeting BCMA and myeloma cells. Then there is no resistance mechanism known because it shuts down basically any transcription and translation of proteins. So it kills cells – resting cells, not only proliferative cells. And it has one big interesting feature, not only killing resting cells, but has a higher sensitivity or efficacy, at least in vitro, for cells that harbor deletion 17p. Why is that? Because locus where the target is coded is right next to the TP53 gene, right, on 17p. And so it’s almost always co-deleted and it increases sensitivity towards alpha-amanitin as a drug, so to say. And we show in this first-in-human trial, in the higher, last tested higher dose cohort now, that we in very, very refractory patients can here already single agent activity achieve with about 50% response rate, and dose escalation is still ongoing, and very, very well tolerated overall. So might be a very interesting drug in the future.
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