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

NCT ID: NCT03136653

Last Updated: 2021-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2021-01-13

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm Study MP0250 plus BOR + DEX

Single arm study of MP0250 plus bortezomib + dexamethasone

Group Type: EXPERIMENTAL

MP0250 plus BOR+DEX

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. 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.

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. Male Participants: A male participant must agree to use a highly effective contraception

13. Female Participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP) OR

2. A WOCBP who agrees to follow contraceptive guidance from the Screening visit, during the treatment period and for at least 3 months after the last dose of study treatment

14. 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. Current participation in any other interventional clinical study

21. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)

22. 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

23. Patients with contraindication to dexamethasone or bortezomib according to the applicable local product label

24. Known hypersensitivity to components of the investigational product, for example, histidine buffer or the Tween diluent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Molecular Partners AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, Vienna, Austria

Landeskliniken Salzburg Saint Johanns-Spital

Salzburg, , Austria

Fakultní Nemocnice Brno

Brno, Jihormoravsky Krav, Czechia

Fakultní Nemocnice Ostrava

Ostrava - Poruba, Severomoravsky KRAJ, Czechia

Odense University Hospital

Odense C, , Denmark

Vejle Sygehus

Vejle, , Denmark

Asklepios Klinik Altona

Altona, City state of Hamburg, Germany

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Universitaetsklinikum Essen

Essen, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Azienda Ospedaliera Policlinico di Bari

Bari, , Italy

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, , Italy

Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich

Chorzów, Silesian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Centrum Onkologii Ziemi Lubelskiej

Lublin, , Poland

Szpital Wojewódzki w Opolu

Opole, , Poland

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Countries

Austria; Czechia; Denmark; Germany; Italy; Poland

Other Identifiers

2016-002771-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MP0250-CP201

Identifier Type: -

Identifier Source: org_study_id