IMS 2024 | Insights into the CA057-003 trial: mezigdomide, tazemetostat & dexamethasone for R/R myeloma

So, this meeting I also had the privilege of communicating as an oral abstract some preliminary results of a trial that is exploring mezigdomide, the latest generation CELMoD, oral agent, in some novel combinations. It is important to understand where that came from. When we go back and study how myeloma become resistant eventually to immunomodulatory drugs, which are the precursors of CELMoDs, there are some pathways that become relevant. One of these is the Ras/Raf pathway, but also the EZH2 pathways that target, which is not necessarily very relevant in myeloma to begin with, becomes very much implicated in resistance to IMiDs and potentially CELMoDs. So it makes sense to combine tazemetostat, which is an existing approved for other indications, EZH2 inhibitor with mezigdomide and dexamethasone. So this was being presented here – the partial results of the dose finding trial. So we have 15 patients with this combination. And this is perhaps one of the most heavily pretreated populations on any myeloma trial. Not only on the number of lines of therapy that’s a medium six, but also on what they got before. At least half those patients have had T-cell redirecting therapy. Many of those have had CAR T-cell, including several patients who have had more than one CAR T-cell. And the results so far look very encouraging. Adding tazemetostat to mezigdomide and dexamethasone does not seem to add much in terms of toxicity. We didn’t see any new toxicity, mostly hematologic toxicity, which is very proportional to what you expect on mezi-dex alone. And we are able to explore all the doses and now they’re found to be safe, so we have a recommended Phase II dose. And the responses have been, you know, nominally better than what you see with mez and dex alone in the less heavily pre-treated population, with as many as two-thirds of the patients responding at the recommended Phase II dose. So we’re very excited about this combination and particularly the prospect of bringing a new class of agents into the myeloma therapeutic armamentarium, now a combination with mezigdomide.