COMy 2022 | Modakafusp alfa: promising results as a first-in-class immunocytokine for R/R multiple myeloma

We were really excited to present our initial results of TAK-573, now known as modakafusp alfa, for patients with relapsed/refractory myeloma, because this is really a brand new type of anti-myeloma agent. It’s not like anything that’s ever been used before for multiple myeloma. It’s an immunologically active cytokine interferon that’s been attenuated and attached to an anti-CD38 antibody backbone that’s different from all the current anti-CD38 antibodies that are currently being used therapeutically for myeloma. So it doesn’t bind to the same place on the CD38 molecule and it’s got an antibody subtype, an IgG4 backbone that’s not immunologically active. So it’s really a way to deliver interferon signaling specifically to cells that carry CD38. And that’s definitely myeloma plasma cells.

And this drug in both in vitro and in vivo models, clearly targets directly at myeloma plasma cells and causes cell death. So it has a direct anti-myeloma cytotoxic effect. But CD38 is also on a variety of immune cells, including NK cells and T-cells. And to those cells, interferon provides a stimulatory signal. And we’ve seen some evidence of this in both preclinical models and from correlative samples taken during our trial, so that we think that modakafusp has the ability to combine a direct anti-myeloma effect with an immune stimulatory signal, that combined can lead to good myeloma responses. And really, that was the most striking finding of our study. Is that in patients with very relapsed/refractory multiple myeloma, we saw 40% responses with single agent modakafusp, at a dose that we think is overall tolerable. It does cause some low platelets and low neutrophil counts, but those seem to be manageable.

And most importantly, mostly were seen during the first cycle of therapy and not later on in treatment. Then the responses were both meaningful and durable. We have patients who have continued to respond nine and 12 months after the initial start of study treatment. And so, we think they’re getting tremendous clinical benefit from modakafusp therapy, and we’re really excited to see where this drug takes us in the future.