Clinical Trials /

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

NCT03136653

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MP0250-CP201
  • SECONDARY ID: 2016-002771-10
  • NCT ID: NCT03136653

Conditions

  • Multiple Myeloma in Relapse

Interventions

DrugSynonymsArms
MP0250 plus BOR+DEXSingle arm Study MP0250 plus BOR + DEX

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Single arm Study MP0250 plus BOR + DEXExperimentalSingle arm study of MP0250 plus bortezomib + dexamethasone
  • MP0250 plus BOR+DEX

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Estimate the efficacy of MP0250 plus BOR + DEX based on overall response rate (ORR)
Time Frame:24 months
Safety Issue:
Description:proportion of patients achieving CR, VGPR or PR according to the IMWG criteria

Secondary Outcome Measures

Measure:Determine the safety profile of MP0250 plus BOR + DEX
Time Frame:24 months
Safety Issue:
Description:type, frequency and severity of adverse events based on CTCAE 4.03
Measure:Determine the immunogenicity of MP0250 plus BOR + DEX
Time Frame:24 months
Safety Issue:
Description:assess anti-drug antibodies
Measure:Determine PFS of MP0250 plus BOR + DEX
Time Frame:24 months
Safety Issue:
Description:Time (months) to date of tumor progression or death
Measure:Determine DOR of MP0250 plus BOR + DEX
Time Frame:24 months
Safety Issue:
Description:duration from first observation of PR to the time of disease progression or death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Molecular Partners AG

Trial Keywords

  • DARPin
  • MP0250
  • VEGF
  • HGF
  • RRMM

Last Updated

February 24, 2020