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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03136653
Recruitment Status : Completed
First Posted : May 2, 2017
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Molecular Partners AG

Brief Summary:

The purpose of this study is to assess the efficacy, safety, tolerability, pharmacokinetics (PK), immunogenicity and biological activity 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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma in Relapse Biological: MP0250 plus BOR+DEX Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-label, Single-arm, Multicenter Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Refractory and Relapsed Multiple Myeloma
Actual Study Start Date : May 23, 2017
Actual Primary Completion Date : October 12, 2020
Actual Study Completion Date : January 13, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Single arm Study MP0250 plus BOR + DEX
Single arm study of MP0250 plus bortezomib + dexamethasone
Biological: MP0250 plus BOR+DEX

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.





Primary Outcome Measures :
  1. Part 1: Overall Response Rate (ORR) [ Time Frame: 24 months ]
    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.

  2. Part 2: ORR [ Time Frame: 24 months ]
    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.


Secondary Outcome Measures :
  1. Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events [ Time Frame: 24 months ]
  2. Number of Participants who Experienced One or More Treatment-Emergent SAEs [ Time Frame: 24 months ]
  3. Number of Participants Who Experienced One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 Adverse Events [ Time Frame: 24 months ]
  4. Number of Participants with a Clinical Significant Change from Baseline in Laboratory Results [ Time Frame: 24 months ]
  5. Number of Participants with a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: 24 months ]
  6. Number of Participants with a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Results [ Time Frame: 24 months ]
  7. Number of Participants with a Positive Anti-drug Antibody (ADA) Result [ Time Frame: 24 months ]
  8. Titer of Anti-drug Antibodies (ADA) [ Time Frame: 24 months ]
  9. Time Course of Anti-drug Antibodies [ Time Frame: 24 months ]
  10. Duration of Response (DOR) [ Time Frame: 24 months ]
    DOR is defined as the duration from first observation of partial response (PR) or better until disease progression, or death from myeloma.

  11. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    PFS is determined as the time from first study treatment until progression or death from myeloma.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with MM who have received:

    • Part 1(Completed) ≥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.
  2. 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.
  3. Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1)
  4. Life expectancy >3 months
  5. 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
  6. Absolute neutrophil count (ANC) ≥1000/mm3 at Screening. Screening ANC must be independent of growth factor support for ≥1 week
  7. 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
  8. 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
  9. Calculated or measured creatinine clearance (CrCl) of ≥ 45 mL/min at Screening based on the Cockcroft and Gault formula
  10. Serum albumin concentration ≥ 25 g/L. Note: Patients with lower levels of serum albumin at baseline may receive albumin supplementation to comply with this criterion.
  11. Males and females ≥18 years of age
  12. Capable of giving signed informed consent

Exclusion Criteria:

  1. 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
  2. Peripheral neuropathy Grade 2 or higher at Screening or patients with a history of Grade 3/4 neuropathy or Grade 2 with pain
  3. 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
  4. 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
  5. Uncontrolled hypertension (defined as systolic blood pressure (SBP) >150 mm Hg diastolic blood pressure (DBP) >100 mm Hg despite antihypertensive medication)
  6. Stroke, or transient ischemic attack within 6 months of Screening, clinically significant bleeding and vascular disease
  7. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  8. Significant concurrent, uncontrolled medical condition including, but not limited to, severe wound healing complication, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
  9. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to screening
  10. Clinical signs of or documented leptomeningeal or cerebral involvement of MM
  11. Treatment with ixazomib as last line of therapy in Part 2
  12. Therapy with approved or investigational anticancer therapeutics within 21 days (or in the case of nitrosureas, within 6 weeks) prior to treatment (except anti-myeloma treatment with a carfilzomib- or bortezomib-based regimen in Part 2) Note: Patients must have recovered from pre-existing, treatment-related adverse events to Grade 1 or lower
  13. Autologous stem cell transplantation (ASCT) within 12 weeks before the date of enrollment
  14. Prior allogeneic stem cell transplantation with active graft-versus-host-disease
  15. Major surgery within 21 days prior to Screening
  16. Immunotherapy within 21 days prior to Screening
  17. Newly initiated therapy with bisphosphonate or RANKL (within two months prior to Screening). Patients on stable regimen with bisphosphonate or receptor activator of nuclear kappa-B ligand (RANKL)-inhibitor therapy over 2 months can continue these treatments at the same dose. No new therapy with bisphosphonate/RANKL inhibitor is allowed during the study
  18. Radiation therapy within 2 months of Cycle 1, Day 1 is not permitted Except for local low-dose, palliative radiation to bone lesions for pain control.
  19. Patients who have received treatment with any non-marketed product within 21 days prior to treatment start
  20. Known infection with human immunodeficiency virus or serologic status reflecting active hepatitis B or hepatitis C virus infection as follows:

    • Not receiving or not responding to anti-viral therapy.
    • HCV RNA detected
  21. Patients with contraindication to dexamethasone or bortezomib according to the applicable local product label
  22. Known hypersensitivity to components of the investigational product, for example, histidine buffer or the Tween diluent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03136653


Locations
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Sponsors and Collaborators
Molecular Partners AG
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Responsible Party: Molecular Partners AG
ClinicalTrials.gov Identifier: NCT03136653    
Other Study ID Numbers: MP0250-CP201
2016-002771-10 ( EudraCT Number )
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Molecular Partners AG:
DARPin
MP0250
VEGF
HGF
RRMM
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases