MP0250 IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED-AND-REFRACTORY MULTIPLE MYELOMA: FIRST SAFETY AND EARLY EFFICACY ANALYSIS OF MP0250-CP201
Author(s): ,
Monika Szarejko
Affiliations:
Medical - Clinical Development,University Clinical Centre ,Gdansk,Poland
,
Stefan Knop
Affiliations:
Department of Medicine II,University Hospital Wurzburg,Wurzburg,Germany
,
Martin Schreder
Affiliations:
Department of Medicine II,University Hospital Wurzburg,Wurzburg ,Germany
,
Harmut Goldschmidt
Affiliations:
Hematology, Oncology and Rheumtology,Heidelberg University Hospital,Heilderberg ,Germany
,
Marc S Raab
Affiliations:
Hematology, Oncology and Rheumtology,Heidelberg University Hospital,Heilderberg ,Germany
,
Artur Jurczyszyn
Affiliations:
Clinical Department of Hematology,University Hospital,Krakow,Poland
,
Norbert Grzasko
Affiliations:
Department of Hematology ,Centre of Oncology of Lublin Region,Lublin ,Poland
,
Jan Duerig
Affiliations:
Department of Hematology ,University Hospital Essen ,Essen,Germany
,
Barbara Gamberi
Affiliations:
Hematology Complex Operative Unit ,Senior Hospital Santa Maria Nuova,Reggio Emilia,Italy
,
Angelo Vacca
Affiliations:
Deparment of Biomedical Sciences and Human Oncology ,University of Bari Medical School,Bari,Italy
,
Roberto Ria
Affiliations:
Deparment of Biomedical Sciences and Human Oncology ,University of Bari Medical School,Bari,Italy
,
Jutta haunschild
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Christof Zitt
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Frank Hermann
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Keith Dawson
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Andreas Harstrick
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Jorge Acosta
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
,
Guy Lemaillet
Affiliations:
Molecular Partners AG,Zurich Schlieren,Switzerland
Sara Bringhen
Affiliations:
Department of Oncology and hematology, Clinical trials in onco-hematology and multiple myeloma,City of Health and Science of Turin,Turin,Italy
EHA Library. Szarejko M. Jun 15, 2018; 215046; PF596
Dr. Monika Szarejko
Dr. Monika Szarejko
Contributions
Abstract

Abstract: PF596

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background

Upregulation of both the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) pathways are implicated in tumor survival, growth, angiogenesis, and loss of response to therapy and linked to poor prognosis in relapsed-and-refractory multiple myeloma (RRMM). MP0250 is a first-in-class, tri-specific multi-DARPin® drug candidate neutralizing VEGF-Α and HGF as well as binding to human serum albumin to increase plasma half-life. MP0250 shows activity in multiple preclinical tumor models including a MM model in which it enhances the effects of bortezomib in terms of M protein production and bone lysis.

Aims

To determine the safety, tolerability, and efficacy of MP0250 in combination with bortezomib and dexamethasone (dex) and the recommended dose for further development in MM.

Methods

This trial (NCT03136653) is recruiting adults ≥18 years of age with RRMM who have progressed after at least two prior treatment regimens including bortezomib and an immunomodulatory drug (IMiD). A dose-escalation phase (part 1) consisting of two cohorts will define a safe dose of the combination of bortezomib + dex and MP0250 followed by a dose expansion phase. Up to 40 patients will be enrolled.  Patients will receive treatment until there is documented disease progression or unacceptable toxicity.

The primary endpoint is efficacy in terms of overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria. Secondary endpoints include safety, immunogenicity, progression free survival (PFS) and duration of response (DOR). Exploratory endpoints include Pharmacokinetics and potential biomarkers. The safety analysis set (SAF) is defined as patients who have received at least 1 dose of combination of MP0250 plus bortezomib + dex.

Results

As of 19 February 2018, 8 patients have been treated with 8 mg/kg MP0250 in cohort 1 and were included in the SAF, with the last patient enrolled on 02 January 2018. Median time from initial diagnosis to first dose of MP0250 was 4.8 years (range, 1-10).  Median number of prior therapies was 3 (range, 2-5).  All 8 patients had been exposed to IMiDs and proteasome inhibitors (PI) and 37.5% were considered PI refractory. The most frequent drug-related grade ≥ 3 AEs included thrombocytopenia in 3 pts (37.5%) and hypertension in 2 pts (25%). Grade 3 proteinuria and transient grade 3 liver enzyme elevation was seen in 1 patient each (12.5%). One dose-limiting toxicity has been reported in cohort 1 (grade 3 hypertension). There were no infusion-related reactions. All patients treated at the 8 mg/kg dose were evaluable for response assessment. At last follow-up, 5 (62.5%) patients had achieved a partial response. Pharmacokinetic data obtained from the first 3 patients are in agreement with results obtained in the phase 1 study with MP0250.

Conclusion

Early data from patients treated in cohort 1 with MP0250 plus bortezomib + dex show an acceptable safety profile and promising activity in RRMM patients. Enrollment is ongoing and updated data from cohorts 1 (8 mg/kg) and 2 (12 mg/kg) will be presented.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Myeloma, VEGF

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