ASCO 2025 | A Phase II trial of modakafusp alfa monotherapy in multiple myeloma

So we did recently publish the results of a Phase II trial of modakafusp alfa for relapsed and refractory multiple myeloma. Modakafusp is a fusion protein targeting CD38, so the same target as our CD38 monoclonal antibodies like daratumumab and isatuximab, but then fused to interferon alpha molecules designed to deliver interferon signaling to CD38-positive cells, which includes both multiple myeloma cells, but also other immune cells like B-cells and T-cells. And one of the interesting things about modakafusp is that although interferon signaling is toxic in multiple myeloma cells and leads to cell death, it’s actually activating for T-cells and NK-cells and certain populations of B-cells so that modakafusp can both be toxic to myeloma cells and can induce immune stimulation in the bone marrow microenvironment at the same time. 

We had previously published the results of our Phase I trial, figuring out what the optimal dose and schedule of modakafusp is, and it’s given intravenously once a month. This Phase II trial was designed to look at two different doses of modakafusp to try to optimize what the best dose would be to move forward in future trials. And what we found confirmed the results of our Phase I trial in that modakafusp is overall relatively well tolerated. Its main side effect that we have to pay attention to is thrombocytopenia. It is remarkably effective as a single agent with an approximately 40% overall response rate. 

What we saw in the Phase II trial was that the higher dose of modakafusp had both a slightly higher overall response rate and a little bit more cytopenias associated with it. So that’s probably the dose that we would pick to move forward in Phase II trials, although if we were trying to treat patients who were especially frail or had very low blood counts, maybe we’d want to use the lower of the two doses. But both doses were effective, and both doses had primarily thrombocytopenia and neutropenia as their main toxicities. 

Unfortunately, Takeda, which had been developing modakafusp, has decided to discontinue its further development, and the future of this drug is a little bit uncertain. We’re still hoping that we’ll be able to move it forward in additional trials in multiple myeloma because it’s so clearly an effective drug and because it works completely differently from anything that’s out there right now.

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