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EHA 2024 | Mezigdomide, dexamethasone and tazemetostat in patients with multiple myeloma in the CA057-003 trial
Luciano Costa, MD, PhD, UAB School of Medicine, Birmingham, AL, presents preliminary findings from a cohort of patients with multiple myeloma (MM) treated with the combination of mezigdomide, dexamethasone and tazemetostat in the CA057-003 trial (NCT05372354). Of the 13 patients treated, data indicate the combination is safe, with no new safety signals compared to single-agent mezigdomide. More than half of the patients responded, marking a promising first step towards an effective mezigdomide-based combination. This interview took place at the 29th Congress of the European Hematology Association (EHA) in Madrid, Spain.
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Transcript
So this is a trial with mezigdomide, which we know is a powerful CELMoD that has very strong single agent activity and activity in combination with dexamethasone, as has been shown in a prior phase two study. We know a CELMoD essentially has a shared some mechanism of action with the immunomodulatory agents and with some very strong pre-clinical work, show some pathways that are associated with resistance to IMiDs and those involves a EZH2, involve BET, and involved the MAP kinase pathway, the RAS/RAF pathway...
So this is a trial with mezigdomide, which we know is a powerful CELMoD that has very strong single agent activity and activity in combination with dexamethasone, as has been shown in a prior phase two study. We know a CELMoD essentially has a shared some mechanism of action with the immunomodulatory agents and with some very strong pre-clinical work, show some pathways that are associated with resistance to IMiDs and those involves a EZH2, involve BET, and involved the MAP kinase pathway, the RAS/RAF pathway.
And so what this study does is it combines in different cohorts mezigdomide at different doses with dexamethasone, with an EZH2 inhibitor, with a BET inhibitor, or with a MEK inhibitor, to try to gain some early data on the safety and preliminary data on activity of this different combination. So what we’re presenting at EHA is the first data disclosure of the first cohort, which is mezig, dexamethasone and tazemetostat, which is the EZH2 inhibitor.
It is a relatively small study 13 patients. How it shows is that this is a very safe combination. And we’re seeing with no new safety signal, looks very much comparable to what you expect from mezig. And the activity was quite impressive in some cases. More than half the patients responded, and that’s particularly impressive considering this is a very heavily pretreated cohort with many, if not most, patients have received, for example, prior BCMA directed therapy. So it’s a first step towards what could be a powerful mezig-based combination in the future.
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