{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:02:10Z","timestamp":1787162530977,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF\u2010A) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>In this open\u2010label, single\u2010arm phase 1b\/2 study (NCT03136653) in patients with proteasome inhibitor\u2010 and\/or immunomodulatory drug\u2010relapsed or refractory MM, MP0250 was administered every 3\u00a0weeks with standard bortezomib\/dexamethasone regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Thirty\u2010three patients received at least one dose of MP0250. The most frequent treatment\u2010related 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\u201375]), 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\u2013NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression\u2010free survival was 4.2 months (95% CI\u00a01.9\u20137.1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jha2.968","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T09:49:44Z","timestamp":1722505784000},"page":"940-950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["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"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1276-6639","authenticated-orcid":false,"given":"Stefan","family":"Knop","sequence":"first","affiliation":[{"name":"Universit\u00e4tsklinikum W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Szarejko","sequence":"additional","affiliation":[{"name":"Uniwersyteckie Centrum Kliniczne  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7727-4307","authenticated-orcid":false,"given":"Norbert","family":"Grz\u0105\u015bko","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematooncology Medical University of Lublin and Centrum Onkologii Ziemi Lubelskiej  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bringhen","sequence":"additional","affiliation":[{"name":"SSD Clinical Trial in Oncoematologia e Myeloma, Dipartimento di Oncologia Azienda Ospedaliera\u2010Universitaria Citt\u00e0 della Salute e della Scienza di Torino Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9050-1049","authenticated-orcid":false,"given":"Karolin","family":"Trautmann\u2010Grill","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Dresden, Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Jurczyszyn","sequence":"additional","affiliation":[{"name":"Plasma Cell Dyscrasias Center, Department of Hematology Jagiellonian University Medical College Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4567-8216","authenticated-orcid":false,"given":"Angelo","family":"Vacca","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area Unit of Medicina Interna \u201cGuido Baccelli\u201d University of Bari Aldo Moro Azienda Policlinico Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-6269","authenticated-orcid":false,"given":"Cyrus","family":"Khandanpour","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum M\u00fcnster, M\u00fcnster, Germany and University Hospital Schleswig\u2010Holstein Campus L\u00fcbeck University Cancer Center Schleswig\u2010Holstein, and University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-5838","authenticated-orcid":false,"given":"Barbara","family":"Gamberi","sequence":"additional","affiliation":[{"name":"AUSL\u2010IRCCS Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludek","family":"Pour","sequence":"additional","affiliation":[{"name":"Fakultn\u00ed Nemocnice Brno Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-9034","authenticated-orcid":false,"given":"Katrine F.","family":"Iversen","sequence":"additional","affiliation":[{"name":"Lillebaelt Hospital Vejle Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-2061","authenticated-orcid":false,"given":"Michael T.","family":"Stumpp","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosima","family":"Suter","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-291X","authenticated-orcid":false,"given":"Keith M.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Zitt","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Legenne","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3000-2205","authenticated-orcid":false,"given":"Vaia","family":"Stavropoulou","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Fey","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Leupin","sequence":"additional","affiliation":[{"name":"Molecular Partners AG Zurich\u2010Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-0035","authenticated-orcid":false,"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Medical Department V Universit\u00e4tsklinikum Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101116"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6619"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30090573"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2022.100929"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15184550"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402875"},{"issue":"4","key":"e_1_2_12_8_1","first-page":"923","article-title":"The HGF\/c\u2010MET axis as a potential target to overcome survival signals and improve therapeutic efficacy in multiple myeloma","volume":"4","author":"Giannoni P","year":"2021","journal-title":"Cancer Drug Resist"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-568881"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.197"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12307-011-0072-9"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050-7771-2-8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12578"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6820241"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.04112.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12270"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0847"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH04-06-0334"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061765"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V114.22.3885.3885"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27745"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-017-2980-3"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2017.1305529"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-020-00429-8"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21738"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24351"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00596"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-299487"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017789"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(22)00290-3"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5753"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303194"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.9074"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0558"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.101939"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3210"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.968","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T05:19:50Z","timestamp":1739337590000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jha2.968"],"URL":"https:\/\/doi.org\/10.1002\/jha2.968","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2024-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}