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

Inclusion criteria

• 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
• 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
• Males and females ≥18 years of age
• Male Participants: A male participant must agree to use a highly effective contraception
• 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:

• Not a woman of childbearing potential (WOCBP) OR
• 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
• Capable of giving signed informed consent

Exclusion criteria

• 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
• 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
• Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to screening
• Clinical signs of or documented leptomeningeal or cerebral involvement of MM
• Treatment with ixazomib as last line of therapy in Part 2
• 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
• Autologous stem cell transplantation (ASCT) within 12 weeks before the date of enrollment
• Prior allogeneic stem cell transplantation with active graft-versus-host-disease
• Major surgery within 21 days prior to Screening
• Immunotherapy within 21 days prior to Screening
• 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
• 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.
• Patients who have received treatment with any non-marketed product within 21 days prior to treatment start
• Current participation in any other interventional clinical study
• Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
• 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
• Patients with contraindication to dexamethasone or bortezomib according to the applicable local product label
• Known hypersensitivity to components of the investigational product, for example, histidine buffer or the Tween diluent