EHA 2025 | Phase I trial of all-oral combination of mezigdomide with three small-molecule inhibitors in RRMM

This is a novel, completely oral, three-cohort study looking at late-line patients. So even with immunotherapies coming, people are still relapsing, we need new options. Mezigdomide is coming for registration of trials in second line, but this is for later lines. So the study is a Phase I study combining mezigdomide with three small molecular inhibitors. Tazemetostat, which is an EZH2 inhibitor, a BET inhibitor, which just has a number, and then trametinib, which is a MEK inhibitor. So we have treated about 20 patients in each of these cohorts. Patients’ majority, over 80%, are triple refractory. Actually over 50%, about I think it’s 55% of patients has received previous immunotherapy with CAR-T or bispecifics. It’s a really, really heavily pretreated group. So what we see very short is that with the follow-up we have now, all cohorts achieve response rates of 60 to 80%, even 100% in some of those cohorts, which is quite impressive in such a heavily pretreated population. It’s equal to the bispecifics when they came in a late-line population. So it looks really good and it’s also completely oral. Not much problematic side effects. Of course, mezigdomide has neutropenia and these patients get infections. But now we will move on based on this data to go into Phase II trials with two of the cohorts. Those are the two cohorts who have the best PFS of about seven months.

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