['multiple myeloma']
['carfilzomib', 'dexamethasone']

        Key Inclusion Criteria:

          1. Relapsed multiple myeloma

          2. Refractory multiple myeloma defined as meeting 1 or more of the following:

               -  Nonresponsive to most recent therapy (stable disease only or PD while on
                  treatment), or

               -  Disease progression within 60 days of discontinuation from most recent therapy

          3. At least 2 but no more than 3 prior therapies for multiple myeloma

          4. Prior exposure to an immunomodulatory agent (IMiD)

          5. Prior exposure to a proteasome inhibitor (PI)

          6. Documented response of at least partial response (PR) to 1 line of prior therapy

          7. Measurable disease with at least 1 of the following assessed within the 21 days prior
             to randomization:

               -  Serum M-protein ≥ 0.5 g/dL

               -  Urine M-protein ≥ 200 mg/24 hours

               -  In subjects without detectable serum or urine M-protein, serum free light chain
                  (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio

          8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

          9. Left ventricular ejection fraction (LVEF) ≥ 40% within the 21 days prior to
             randomization

         10. Adequate organ and bone marrow function within the 21 days prior to randomization
             defined by:

               -  Bilirubin < 1.5 times the upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the
                  ULN

               -  Absolute neutrophil count (ANC) ≥ 1000/mm³ (screening ANC should be independent
                  of growth factor support for ≥ 1 week)

               -  Hemoglobin ≥ 8.0 g/dL (Use of erythropoietic stimulating factors and red blood
                  cell [RBC] transfusion per institutional guidelines is allowed, however the most
                  recent RBC transfusion may not have been done within 7 days prior to obtaining
                  screening hemoglobin.)

               -  Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ if myeloma involvement in the bone
                  marrow is > 50%. Subjects should not have received platelet transfusions for at
                  least 1 week prior to obtaining the screening platelet count.)

               -  Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min

        Key Exclusion Criteria:

          1. Waldenström macroglobulinemia

          2. Multiple myeloma of Immunoglobin M (IgM) subtype

          3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          4. Plasma cell leukemia (> 2.0 × 10⁹/L circulating plasma cells by standard differential)

          5. Myelodysplastic syndrome

          6. Second malignancy within the past 5 years except:

               -  Adequately treated basal cell or squamous cell skin cancer

               -  Carcinoma in situ of the cervix

               -  Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA)
                  over 12 months

               -  Ductal breast carcinoma in situ with full surgical resection (i.e., negative
                  margins)

               -  Treated medullary or papillary thyroid cancer

               -  Similar condition with an expectation of > 95% five-year disease-free survival

          7. History of or current amyloidosis

          8. Cytotoxic chemotherapy within the 28 days prior to randomization

          9. Immunotherapy within the 21 days prior to randomization

         10. Glucocorticoid therapy within the 14 days prior to randomization that exceeds a
             cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone

         11. Radiation therapy:

               -  Focal therapy within the 7 days prior to randomization

               -  Extended field therapy within the 21 days prior to randomization

         12. Prior treatment with either carfilzomib or oprozomib

         13. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
             carfilzomib)

         14. Contraindication to dexamethasone or any of the required concomitant drugs or
             supportive treatments, including hypersensitivity to antiviral drugs, or intolerance
             to hydration due to pre-existing pulmonary or cardiac impairment

         15. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV),
             symptomatic ischemia, conduction abnormalities uncontrolled by conventional
             intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or
             myocardial infarction within 6 months prior to enrollment

         16. Active infection within the 14 days prior to randomization requiring systemic
             antibiotics

         17. Pleural effusions requiring thoracentesis within the 14 days prior to randomization

         18. Ascites requiring paracentesis within the 14 days prior to randomization

         19. Ongoing graft-versus-host disease

         20. Uncontrolled hypertension or uncontrolled diabetes despite medication

         21. Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization

         22. Known cirrhosis
      