Study of Modakafusp Alfa in Relapsed Multiple Myeloma Patients

Dr. Dan Vogl presents the final results from the phase 1/2 first-in-human study of Modakafusp Alfa, in patients with relapsed/refractory myeloma

Abstract title:

Final Results from the First-in-Human Phase 1/2 Study of Modakafusp Alfa, an Immune-Targeting Attenuated Cytokine, in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)

Purpose of the trial:

Modakafusp alfa is a first-in-class, immune-targeting, attenuated cytokine. It consists of 2 attenuated interferon (IFN)α2b molecules genetically fused to the Fc portion of an anti-CD38 IgG4 monoclonal antibody (mAb), allowing targeted delivery of IFNα to innate and adaptive immune cells, as well as myeloma cells. We previously reported preliminary results from a cohort of 30 pts who received modakafusp 1.5 mg/kg every 4 weeks (Q4W) in this phase 1/2 study (NCT03215030) (Kaufman EHA 2022, S181). We now report the final safety and efficacy results of the study (parts 1 and 2), including minimal residual disease (MRD) status.

Video summary:

Pts had received ≥3 prior lines of treatment and were refractory to or intolerant of ≥1 proteasome inhibitor and ≥1 immunomodulatory drug. During dose escalation, modakafusp was administered intravenously at 10 dose levels between 0.001–6 mg/kg; weekly (QW; cycles 1–2 only; 0.001–0.75 mg/kg), every 2 weeks (Q2W; 0.2–0.3 mg/kg), every 3 weeks (Q3W; 0.4–0.75 mg/kg), or Q4W (0.75–6 mg/kg). As anti-myeloma response was detected during dose escalation, expansion cohorts were opened at 0.4 mg/kg Q3W and 1.5 mg/kg Q4W as a single agent. As dexamethasone (dex) is part of standard of care in MM, but could counteract the immune activation elicited by modakafusp, additional cohorts at 0.4 mg/kg Q3W and 1.5 mg/kg Q4W in combination with 40 mg dex QW were opened. Bone marrow aspirates (BMA) for MRD evaluation were collected at screening and at suspected CR and were assessed utilizing the clonoSEQ® next generation sequencing assay at a threshold of 10-5. Peripheral blood samples were collected and evaluated for CD38 receptor density determination by flow cytometry.

Conclusions:

Modakafusp alfa has a novel mechanism of action, a manageable safety profile, and encouraging anti-myeloma activity at 1.5 mg/kg Q4W, independent of peripheral blood immune cell CD38 expression. A randomized phase 2 study to compare fixed-dose levels of 120 and 240 mg (equivalent to 1.5 and 3.0 mg/kg) Q4W and to define the single-agent dose with the optimal benefit/risk profile is currently enrolling.

Trial information:

ASH 2022: Abstract #565

Authors:

Dan T. Vogl, MD, Shebli Atrash, MD, Sarah A. Holstein, MD, PhD, Omar Nadeem, MD, Don M. Benson Jr., MD, Kaveri Suryanarayan, MD, Yuyin Liu, Sabrina Collins, Xavier Parot, MD and Jonathan L. Kaufman, MD