A Study of Oprozomib, Pomalidomide, and Dexamethasone in Adults With Primary Refractory or Relapsed and Refractory Multiple Myeloma

Key Inclusion Criteria:

Multiple myeloma that is primary refractory or relapsed and refractory after at least 2 lines of standard for multiple myeloma including:

≥ 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination)
In the dose-expansion and Phase 3 portions of the study only: In addition to the above, treatment with adequate alkylator therapy, defined as:

i. High-dose melphalan or other alkylating agent as conditioning for autologous or allogeneic stem cell transplant (SCT), or ii. ≥ 6 cycles of induction therapy, or iii. Progressive disease after ≥ 2 cycles

Disease progression on or within 60 days of completion of the last therapy

Measurable disease as indicated by 1 or more of the following:

Serum M-protein ≥ 500 mg/dL
Urine M-protein ≥ 200 mg/24 h
For patients without measurable serum or urine M protein, serum free light chain (SFLC): Involved free light chain (FLC) concentration ≥ 10 mg/dL provided SFLC ratio is abnormal
Males and females ≥ 18 years old
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Key Exclusion Criteria:

Systemic chemotherapy with approved or investigational anticancer therapeutics, intended to treat underlying malignancy, within 3 weeks before the first dose or 6 weeks for antibody therapy
Dexamethasone at cumulative doses greater than 160 mg or equivalent within 21 days prior to the first dose of study treatment is not allowed. Use of topical or inhaled steroids is acceptable.
Radiation therapy within 3 weeks before first dose. Radioimmunotherapy within 8 weeks before first dose.
Plasmapheresis is not permitted at any time during the Screening period or while the subject is receiving study treatment. If a subject has started Screening procedures requiring plasmapheresis, or is anticipated to require plasmapheresis during or after the Screen
Autologous SCT within 8 weeks or allogeneic SCT within 16 weeks prior to initiation of study treatment. Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (as defined in Filipovich 2005).
Known hypersensitivity to any immunomodulatory drugs (IMiDs), including Grade 4 rash
Prior treatment of any duration with pomalidomide
Known hypersensitivity or intolerance to dexamethasone
Prior exposure to oprozomib
Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose.