A Phase 2 Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Multiple Myeloma

NCT03136653 | Completed Phase 1 DMC

• 2 other identifiers: MP0250-CP2012016-002771-10
• Study Type: interventional
• Target: 33
• Locations: 6 countries
• Sites: 24

Brief Summary

The purpose of this study is to assess the efficacy, safety, tolerability, pharmacokinetics (PK), immunogenicity and efficacy of MP0250 in combination with bortezomib + dexamethasone in patients with refractory and relapsed multiple myeloma (RRMM). MP0250 is a multi-DARPin® drug candidate with three specificities, able to simultaneously neutralize the activities of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and also to bind to human serum albumin (HSA) to give an increased plasma half-life and potentially enhanced tumor penetration.

Conditions

Multiple Myeloma in Relapse

Keywords

DARPin; MP0250; VEGF; HGF; RRMM

Outcome Measures

Primary Outcomes (2)

• Part 1: Overall Response Rate (ORR)

  Defined as the number of participants achieving a complete response (CR), very good partial response (VGPR), or partial response (PR) during treatment with MP0250 plus bortezomib+dexamethasone determined by the Investigator in part 1.

  24 months

• Part 2: ORR

  Defined as the number of participants achieving a confirmed, stringent complete response (sCR), very good partial response (VGPR), or partial response (PR) during treatment with MP0250 plus bortezomib+dexamethasone determined by the Investigator in part 2.

  24 months

Secondary Outcomes (11)

• Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events

  24 months

• Number of Participants who Experienced One or More Treatment-Emergent SAEs

  24 months

• Number of Participants Who Experienced One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 Adverse Events

  24 months

• Number of Participants with a Clinical Significant Change from Baseline in Laboratory Results

  24 months

• Number of Participants with a Clinically Significant Change from Baseline in Vital Signs

  24 months

Study Arms (1)

Single arm Study MP0250 plus BOR + DEX

EXPERIMENTAL

Single arm study of MP0250 plus bortezomib + dexamethasone

Biological: MP0250 plus BOR+DEX

Interventions

MP0250 plus BOR+DEX BIOLOGICAL

6 mg/kg or 8 mg/kg or 12 mg/kg of MP0250, IV (in the vein,) on day 1 of each 21 day cycle. Bortezomib and Dexamethasone according to label. Number of Cycles: until progression or unacceptable toxicity develops.

Single arm Study MP0250 plus BOR + DEX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with MM who have received:
• Part 1 ≥2 lines of therapy (including bortezomib and an IMiD) and have shown no response (i.e. stable disease) to, have progressed on the most recent treatment or have progressed within 60 days of the most recent therapy
• Part 2 ≥2 lines of prior therapy that included a proteasome inhibitor (bortezomib, carfilzomib or both) and an IMiD (thalidomide, lenalidomide and/or pomalidomide) either alone or in combination and a response no better than SD lasting at least 4 months on a bortezomib- or carfilzomib-based regimen as last line of therapy or progression on treatment or within 60 days of stopping a bortezomib- or carfilzomib-based regimen as last line of therapy. Note: For transplant-eligible patients enrolled to Part 1 or Part 2, induction plus conditioning chemotherapy/ASCT +/- maintenance therapy constitute one regimen.
• Presence of a measurable disease with at least one of the following criteria:
• Serum M protein ≥0.5 g/dL, or
• Urine M protein ≥200 mg/24 h, or
• Involved serum free light chain (FLC) levels \>100 mg/L and abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine M protein, or
• For patients with immunoglobulin A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥0.5g/dL.
• Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1)
• Life expectancy \>3 months
• Adequate hepatic function at Screening, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3x ULN and total bilirubin \<2 x upper limit of normal (ULN). For patients with Gilbert's syndrome (Gilbert-Meulengracht syndrome), higher bilirubin of 5 x ULN is acceptable
• Absolute neutrophil count (ANC) ≥1000/mm3 at Screening. Screening ANC must be independent of growth factor support for ≥1 week
• Hemoglobin ≥8.0 g/dL at Screening. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however most recent RBC transfusion must not have been done within 7 days prior to obtaining screening hemoglobin
• Platelet count ≥50 000/mm3 at Screening. Patients must not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count
• Calculated or measured creatinine clearance (CrCl) of ≥ 45 mL/min at Screening based on the Cockcroft and Gault formula

You may not qualify if:

• Patients with the following diseases:
• Monoclonal gammopathy of undetermined significance (MGUS) of non- immunoglobulin (Ig)M and IgM subtypes,
• Light chain MGUS,
• Solitary plasmacytoma (alone or with minimal marrow involvement),
• Systemic Ig light chain amyloidosis,
• Waldenstrom's Macroglobulinemia,
• Myelodysplastic syndrome,
• Plasma cell leukemia defined as a plasma cell count \>2000/mm3
• Polyneuropathy, organomegaly endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome
• Peripheral neuropathy Grade 2 or higher at Screening or patients with a history of Grade 3/4 neuropathy or Grade 2 with pain
• Prior or concurrent malignancy, except for: Adequately treated basal cell or squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance or any other cancer from which the patient has been disease-free for \>5 years
• Active congestive heart failure (New York Heart Association \[NYHA\] Class III to IV), symptomatic cardiac ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to screening
• Uncontrolled hypertension (defined as systolic blood pressure (SBP) \>150 mm Hg diastolic blood pressure (DBP) \>100 mm Hg despite antihypertensive medication)
• Stroke, or transient ischemic attack within 6 months of Screening, clinically significant bleeding and vascular disease
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (24)

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, Vienna, 1140, Austria

Location

Landeskliniken Salzburg Saint Johanns-Spital

Salzburg, 5020, Austria

Location

Fakultní Nemocnice Brno

Brno, Jihormoravsky Krav, 625 00, Czechia

Location

Fakultní Nemocnice Ostrava

Ostrava - Poruba, Severomoravsky KRAJ, 708 52, Czechia

Location

Odense University Hospital

Odense C, 5000, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

Asklepios Klinik Altona

Altona, Hamburg, 22763, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Azienda Ospedaliera Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich

Chorzów, Silesian Voivodeship, 41-500, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-501, Poland

Location

Centrum Onkologii Ziemi Lubelskiej

Lublin, 20-090, Poland

Location

Szpital Wojewódzki w Opolu

Opole, 45-061, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

MeSH Terms

Interventions

MP0250

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 2, 2017
• Study Start: May 23, 2017
• Primary Completion: October 12, 2020
• Study Completion: January 13, 2021
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); DK (2); IT (5); CZ (2); DE (7); PL (6)