IMS 2025 | Advances in the research of mezigdomide for multiple myeloma: the SUCCESSOR-1 and SUCCESSOR-2 trials

In the context of mezigdomide therapy, we’re really excited. We had both poster presentations at SOHO recently in Houston, Texas, and also here at the meeting at IMS. And in these studies, we’ve shown consistently the value of mezigdomide as an oral therapy, a really potent so-called CELMoD or degrader, modulating the cereblon and E3 ligase complex and by so doing, degrading key transcription factors that are fundamental to myeloma pathobiology, in particular, Ikaros and Aiolos. And as a result, not only directly killing the myeloma cell, but activating the patient’s immune system against the myeloma. So we love to sort of call it CAR-T in a pill. I mean, it’s basically a medicine that can be given orally and activate the immune system in a way that can be very beneficial and recognizing, of course, that it’s obviously a relatively non-toxic approach with myelosuppression being its major challenge, in particular neutropenia. But beyond that, mezigdomide is not only exquisitely active, but also generally very well tolerated. So, the mezigdomide story continues to build because obviously when I say CAR-T in a pill, I’m obviously exaggerating for emphasis, but nonetheless, combined with other drugs, it’s particularly favorable. So, what we showed at SOHO was the results of combining the mezigdomide with the proteasome inhibitor bortezomib, and separately, the results of combining the mezigdomide with carfilzomib. And this really has been a synergistic platform for both approaches, with response rates between 80% and 90%, essentially, for both strategies. And this, I think, in the relapsed refractory setting is remarkable. And its durability of response and the quality of response as well as tolerability was particularly encouraging. These two studies, of course, inform the so-called SUCCESSOR-1 and SUCCESSOR-2 Phase III studies that are currently ongoing with SUCCESSOR-2 fully enrolled and SUCCESSOR-1 probably to be fully enrolled by early next year. And we’re very hopeful that these will then lead to regulatory approvals as early as potentially next year so that we can really provide access for patients to this, to my opinion, this remarkably active class of drug. I think in that spirit, the novel novel combination led by my colleague Luciano Costa, we also discussed at SOHO and is also being discussed here at IMS, where the drug mezigdomide combined with dexamethasone is combined with various other novel agents, including tazemetostat and trametinib, with these being novel targets in myeloma pathobiology. And to cut a long story short, remarkable results, excellent tolerability even in the face of heavily pretreated patients who are actually also so-called BCMA refractory. By that I mean not just antibody drug conjugate exposed but also have had T-cell redirection and even cellular therapies such as CAR-T unfortunately run out of benefit for them and then to get these all oral combinations with significant clinical benefits seen. So very encouraging data for mezigdomide all around.

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