Evidence map›Paper›PMID 39415900›Full record

ArticleEJHaem2024

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 and 10 more

Registry-linked trialAbstract read
In one paragraph

Article in EJHaem, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03136653 (A Phase 2 Open-label, Single-arm, Multicenter Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Refractory and Relapsed Multiple Myeloma), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03136653 phase1 / phase2completednot on this map

A Phase 2 Open-label, Single-arm, Multicenter Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Refractory and Relapsed Multiple Myeloma

TypeinterventionalSponsorMolecular Partners AGRan2017 to 2021Enrolled33ConditionsMultiple Myeloma in RelapseArmsMP0250 plus BOR+DEX
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Stefan KnopUniversitätsklinikum Würzburg Würzburg Germany.ORCID https://orcid.org/0000-0003-1276-6639
Monika SzarejkoUniwersyteckie Centrum Kliniczne Gdansk Poland.
Norbert GrząśkoDepartment of Experimental Hematooncology Medical University of Lublin and Centrum Onkologii Ziemi Lubelskiej Lublin Poland.ORCID https://orcid.org/0000-0001-7727-4307
Sara BringhenSSD Clinical Trial in Oncoematologia e Myeloma, Dipartimento di Oncologia Azienda Ospedaliera-Universitaria Città della Salute e della Scienza di Torino Torino Italy.
Karolin Trautmann-GrillUniversitätsklinikum Dresden, Technische Universität Dresden Dresden Germany.ORCID https://orcid.org/0000-0002-9050-1049
Artur JurczyszynPlasma Cell Dyscrasias Center, Department of Hematology Jagiellonian University Medical College Krakow Poland.
Angelo VaccaDepartment of Precision and Regenerative Medicine and Ionian Area Unit of Medicina Interna "Guido Baccelli" University of Bari Aldo Moro Azienda Policlinico Bari Italy.ORCID https://orcid.org/0000-0002-4567-8216
Cyrus KhandanpourUniversitätsklinikum Münster, Münster, Germany and University Hospital Schleswig-Holstein Campus Lübeck University Cancer Center Schleswig-Holstein, and University of Lübeck Lübeck Germany.ORCID https://orcid.org/0000-0003-4655-6269
Barbara GamberiAUSL-IRCCS Reggio Emilia Reggio Emilia Italy.ORCID https://orcid.org/0000-0003-3616-5838
Ludek PourFakultní Nemocnice Brno Brno Czechia.
Katrine F IversenLillebaelt Hospital Vejle Denmark.ORCID https://orcid.org/0000-0003-4494-9034
Michael T StumppMolecular Partners AG Zurich-Schlieren Switzerland.ORCID https://orcid.org/0000-0001-7356-2061
Cosima SuterMolecular Partners AG Zurich-Schlieren Switzerland.
Keith M DawsonMolecular Partners AG Zurich-Schlieren Switzerland.ORCID https://orcid.org/0000-0002-1770-291X
Christof ZittMolecular Partners AG Zurich-Schlieren Switzerland.
Philippe LegenneMolecular Partners AG Zurich-Schlieren Switzerland.
Vaia StavropoulouMolecular Partners AG Zurich-Schlieren Switzerland.ORCID https://orcid.org/0000-0002-3000-2205
Martin F FeyMolecular Partners AG Zurich-Schlieren Switzerland.
Nicolas LeupinMolecular Partners AG Zurich-Schlieren Switzerland.
Hartmut GoldschmidtMedical Department V Universitätsklinikum Heidelberg Heidelberg Germany.ORCID https://orcid.org/0000-0003-0961-0035

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

anti‐HGFanti‐VEGFDARPinMP0250refractory/relapsed multiple myeloma

Identifiers

PMID39415900
PMCPMC11474421

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.