A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma
Stefan Knop,
Monika Szarejko,
Norbert Grząśko,
Sara Bringhen,
Karolin Trautmann‐Grill,
Artur Jurczyszyn,
Angelo Vacca,
Cyrus Khandanpour,
Barbara Gamberi,
Ludek Pour,
Katrine F. Iversen,
Michael T. Stumpp,
Cosima Suter,
Keith M. Dawson,
Christof Zitt,
Philippe Legenne,
Vaia Stavropoulou,
Martin F. Fey,
Nicolas Leupin,
Hartmut Goldschmidt
Affiliations
Stefan Knop
Universitätsklinikum Würzburg Würzburg Germany
Monika Szarejko
Uniwersyteckie Centrum Kliniczne Gdansk Poland
Norbert Grząśko
Department of Experimental Hematooncology Medical University of Lublin and Centrum Onkologii Ziemi Lubelskiej Lublin Poland
Sara Bringhen
SSD Clinical Trial in Oncoematologia e Myeloma, Dipartimento di Oncologia Azienda Ospedaliera‐Universitaria Città della Salute e della Scienza di Torino Torino Italy
Karolin Trautmann‐Grill
Universitätsklinikum Dresden, Technische Universität Dresden Dresden Germany
Artur Jurczyszyn
Plasma Cell Dyscrasias Center, Department of HematologyJagiellonian University Medical CollegeKrakow Poland
Angelo Vacca
Department of Precision and Regenerative Medicine and Ionian Area Unit of Medicina Interna “Guido Baccelli”University of Bari Aldo MoroAzienda Policlinico BariItaly
Cyrus Khandanpour
Universitätsklinikum Münster, Münster, Germany and University Hospital Schleswig‐Holstein Campus LübeckUniversity Cancer Center Schleswig‐Holstein, and University of LübeckLübeck Germany
Barbara Gamberi
AUSL‐IRCCS Reggio EmiliaReggio EmiliaItaly
Ludek Pour
Fakultní Nemocnice BrnoBrnoCzechia
Katrine F. Iversen
Lillebaelt HospitalVejleDenmark
Michael T. Stumpp
Molecular Partners AGZurich‐Schlieren Switzerland
Cosima Suter
Molecular Partners AGZurich‐Schlieren Switzerland
Keith M. Dawson
Molecular Partners AGZurich‐Schlieren Switzerland
Christof Zitt
Molecular Partners AGZurich‐Schlieren Switzerland
Philippe Legenne
Molecular Partners AGZurich‐Schlieren Switzerland
Vaia Stavropoulou
Molecular Partners AGZurich‐Schlieren Switzerland
Martin F. Fey
Molecular Partners AGZurich‐Schlieren Switzerland
Nicolas Leupin
Molecular Partners AGZurich‐Schlieren Switzerland
Hartmut Goldschmidt
Medical Department V Universitätsklinikum Heidelberg HeidelbergGermany
Abstract MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF‐A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open‐label, single‐arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor‐ and/or immunomodulatory drug‐relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen. Thirty‐three patients received at least one dose of MP0250. The most frequent treatment‐related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44–75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5–NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression‐free survival was 4.2 months (95% CI 1.9–7.1). These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.
