ASH 2025 | Phase II dose optimization study of inobrodib with pomalidomide and dexamethasone in R/R myeloma

This is a phase two dose optimization trial looking at the combination of inobrodib, which is an oral p300 inhibitor in combination with pomalidomide and dexamethasone. And importantly, this drug was shown to have synergy with these immunomodulatory agents in preclinical models as well as additional earlier clinical trials. What was really exciting about this trial is that it included very heavily pretreated patients. So patients that had had, of course, multiple lines of therapy, many were pentarefractory exposed and are refractory, but also 60% of patients or so had also received a prior T-cell engager. Several patients had also received prior CAR-T and prior antibody-drug conjugates. So this is a very heavily pretreated group of patients who really had exhausted standard therapies. 

So inobrodib was given in combination with pomalidomide and dexamethasone at three doses, 20 milligrams, 30 milligrams, and 40 milligrams. What we saw, even in this very heavily-treated population was very encouraging overall response rates ranging from 40 to 60 percent across these dose levels. This is an all oral regimen. This is relatively well tolerated in terms of some of the adverse events that we were seeing. A majority of those were hematologic cytopenias that we see commonly in this patient population outside of cytopenias. We were seeing very tolerable side effects in terms of fatigue, some GI side effects, non-neutropenic fever. Infection rate was not particularly high. So again, a pretty well-tolerated regimen in this heavily pretreated population. And importantly, when you look at severe treatment emergent adverse events, these were higher at the 40 milligram dose. So when we look down at the 20 milligram dose, we were still seeing good efficacy without such high rates of AEs. And so moving forward, the plan is to move forward with the 20 milligram dose. 

So I think really encouraging results for an all-oral regimen. I think in this era of, we have so many, we’re so fortunate to have so many really effective T-cell engager therapies, but we know that we can’t really do these therapies effectively back to back. We still need, there’s still an evident need for effective, well-tolerated therapies that we can use post-T-cell engager or maybe even in between T-cell engagers. I think this is a really important space potentially that inobrodib could fill. And so moving forward, we’re looking forward to the DoMMino-1 trial, which will be a phase two randomized study looking at Inobratib at 20 milligrams in combination with pomalidomide and dexamethasone.

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