Despite recent advances in the treatment of multiple myeloma (MM), patients eventually relapse, requiring multiple lines of treatment. Upregulation of both the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) pathways has been implicated in loss of response to therapy and linked to poor prognosis through different mechanisms such as stimulation of angiogenesis, bone destruction, and myeloma cell proliferation and migration. MP0250 is a first-in-class, tri-specific multi-DARPin® drug candidate neutralizing VEGF and HGF as well as binding to human serum albumin to increase plasma half-life. MP0250 shows activity in multiple preclinical tumor models amongst them an MM model in which it enhances the effects of bortezomib on e.g. M protein production and bone lysis. MP0250 has shown a favorable safety profile in a Phase 1 clinical trial in advanced solid tumors.
This trial is recruiting adults ≥18 years of age with RRMM who have received ≥2 lines of therapy (including bortezomib and an immunomodulatory drug [IMiD]), have not shown any response to and have progressed on or within 60 days of the most recent treatment. The primary endpoint is efficacy in terms of overall response rate (ORR). Secondary endpoints include safety and immunogenicity. A total of 40 patients will be enrolled, 12 patients during a lead-in phase (Part 1) to establish a safe dose and an additional 28 patients in Part 2 to make a total of 34 patients at the target dose. Patients will receive study treatments (MP0250 in combination with bortezomib + dexamethasone) until the end of the study, disease progression, unacceptable toxicity, or other criteria for discontinuation, whichever occurs earlier. Cytogenetic analyses, response assessment, exploratory biomarkers, pharmacokinetics and immunogenicity will be determined in either bone marrow and/or blood/urine. The trial is currently recruiting patients.
Clinical trial identification
EUDRACT number: 2016-002771-10
Legal entity responsible for the study
Molecular Partners AG
Molecular Partners AG
M.S. Raab, R. Ria, J. Schlenzka, A. Vacca, H. Goldschmidt: Has been involved in design of the trial and received study funds through the university for performing the Trial. T. Krahnke: TK has been involved in statistical design of the trial and received consultancy funds. J. Haunschild, F. Herrmann, U. Fiedler, K. Dawson: JH is a full-time employee of Molecular Partners AG. M.T. Stumpp, A. Harstrick: CSO of Molecular Partners AG. K. Tadjalli Mehr: Medical consultant to Molecular Partners AG.