Pharmacokinetic Results and Next Steps for Mezigdomide Combos in RRMM

Paul Richardson, MD, director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts, RJ Corman professor of medicine at Harvard Medical School, further discusses the data from the CC-92480-MM-002 trial (NCT03989414) and future directions for research of mezigdomide (CC-92480) combinations in relapsed/refractory multiple myeloma.

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0:09 | What about pharmacodynamics? Well, we were very pleased to see that [mezigdomide], daratumumab [Darzalex], and dexamethasone were active in T and natural killer [NK] cells in all 3 schedules in both doses. This was very reassuring. There were interesting trends of scheduled dependent T-cell effects, observed both with .3 and .6 mg [with mezigdomide, daratumumab, and dexamethasone]. There was a wonderful presentation by my colleague which is similarly well received, and was focused on this in more detail. But the takeaway here clearly is that there is powerful activity from the drug, even at lower doses. The same story was apparent for elotuzumab/mezigdomide demand. And what you can see here is that there was pharmacodynamic activity for both T and NK cells for the elotuzumab platform, which of course is very important, recognizing that elotuzumab is an excellent platform for natural killer cell activity. S

1:02 | Overall conclusions and future directions are summarized here. Mezigdomide in combination with monoclonal antibodies showed promising efficacy in patients with relapsed/refractory myeloma. We were particularly struck by the 89% response rate in cohort B3. We were similarly very struck by the duration of response. Elotuzumab was very safe and well-tolerated, and also active, even in CD38 with an overall response rate of 45%. Recognizing the relatively small numbers has to be seen with some caution, but I would stress, however, that this clearly for a CD38 refractory population was still, we feel, encouraging.

1:40 | I think what is so important is the outpatient utility of this regimen. At the same time, the safety profile was clearly manageable. It's very consistent with what we saw before. I think what is exciting is that mezigdomide was clearly immunostimulatory in combination with daratumumab at all schedules and dose levels tested. This, I think, is important. I think they support essentially moving mezigdomide into combination with immune therapies, and not just restricted to CD38 and SLAMF7, which are the respective targets, so isatuximab [Sarclisa], daratumumab, elotuzumab, but also BCMA and GPRC5D targeting approaches as well. Indeed, in addition to others, I think the flexible doses and schedules in relapsed/refractory myeloma that we have established with this study provide us with a great platform going forward.

2:27 | I just want to stop here by acknowledging our patients and families above all, and all the clinical teams involved in the study as well as our sponsors, Celgene, [Bristol Myers Squibb], and our list here of course, all the investigators in our study. It is a wonderful international group, as you can see, and thank you very much for your kind attention.