Modakafusp alfa (previously known as TAK-573) is a first-in-class immunocytokine designed to deliver interferon alpha-2b (IFNα2b) to CD38+ cells. It consists of two attenuated IFNα2b molecules genetically fused to the Fc portion of a humanized, anti-CD38, IgG4 monoclonal antibody (mAb). The specificity for CD38 and reduced IFN receptor binding affinity of the attenuated IFNα2b molecules significantly reduces the potential for off-target binding and toxicity. Furthermore, modakafusp alfa binds to a different epitope on CD38 than the currently approved anti-CD38 therapeutic mAbs, daratumumab and isatuximab. Preclinical evaluation of modakafusp alfa supports activation of type I IFN signaling in CD38+ cells, inducing direct anti-proliferative effects on myeloma cells, as well as direct and indirect immune cell activation. We have previously reported preliminary results from the first 59 patients (pts) in our first-in-human phase 1 trial of modakafusp alfa in pts with relapsed/refractory multiple myeloma (RRMM; NCT03215030), showing responses to single-agent therapy with doses starting at 0.1 mg/kg weekly; thrombocytopenia and neutropenia were dose-limiting toxicities when modakafusp alfa was administered weekly (QW), every 2 weeks (Q2W), and every 3 weeks (Q3W) (Vogl, Blood 2020). Here we report updated results from this trial, focusing on results from an expansion cohort with dosing every 4 weeks (Q4W).

Conclusion

Modakafusp alfa (TAK-573) is a novel candidate for the treatment of RRMM, which has shown promising anti-myeloma activity in heavily pretreated pts, including anti-CD38 mAb-refractory pts and those who have received an anti-CD38 mAb in their most recent line of treatment. A Q4W dosing schedule of modakafusp alfa is feasible and the optimal dose and potential combinations are being explored.

ASH 2021: Abstract 898