DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, defined as any of the following treatment-related events occurring within 4 weeks after the first dose of therapy:

Any grade ≥ 3 nonhematologic toxicity, except: Grade 3 asymptomatic electrolyte abnormalities or hypophosphatemia for < 24 hours; Grade 3 nausea, vomiting or diarrhea unless for > 3 days despite optimal supportive care; Grade 3 fatigue for < 14 days; Grade ≥ 3 hyperglycemia or toxicity attributed to dexamethasone and Grade ≥ 3 rash attributed to pomalidomide.

Hematologic toxicities:

• Grade 4 neutropenia: Absolute neutrophil count < 0.5 × 10^9/L for ≥ 7 days despite adequate growth factor support; febrile neutropenia
• Thrombocytopenia: Grade 4 for ≥ 7 days, or Grade 4 for < 7 days with grade 2 clinically significant bleeding or < 10,000 platelets requiring transfusion, or Grade 3 with clinically significant bleeding or requiring platelet transfusion.

Participants who received at least 1 dose of any study drug

Adverse events (AEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE.

A serious AE is an event that met 1 or more of the following criteria:

• Death
• Life-threatening experience
• Required inpatient hospitalization or prolongation of an existing hospitalization
• Resulted in persistent or significant disability/incapacity
• A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject
• Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above.

Treatment-related AEs (TRAE) are those considered related to at least 1 study drug by the investigator.

Participants who received at least 1 dose of any study drug

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

PR: ≥ 50% reduction of serum M-protein and ≥90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥50% decrease in the difference between involved and uninvolved free light chain levels (dFLC). A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by serum FLC (SFLC), ≥ 90% decrease in dFLC.

CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow (BM). Normal SFLC ratio if disease measurable only by SFLC.

sCR: As for CR, and absence of clonal plasma cells in BM.

Participants who received at least 1 dose of any study drug

Clinical benefit rate is defined as the percentage of participants with a best overall response of minimal response (MR) per modified European Group for Blood and Marrow Transplantation criteria, or PR, VGPR, CR, or sCR as determined by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC).

MR:

• ≥ 25% but < 49% reduction in serum M-protein and a 50 - 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg per 24 hours
• If the serum and urine M-protein were not measurable, a decrease of 25 - 49% in the difference between involved and uninvolved FLC levels was required in place of the M-protein criteria.
• For patients with nonsecretory myeloma only, 25 - 49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed
• 25 - 49% reduction in the size of soft tissue plasmacytomas (by radiography or clinical examination)

Participants who received at least 1 dose of any study drug

Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

Participants with adequate oprozomib plasma concentration-versus-time data to allow estimation of pharmacokinetic (PK) parameters. Treatment groups receiving the same dose of oprozomib were combined for PK analyses.

Laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).

Full chemistry panel included sodium, potassium, calcium, alkaline phosphatase, blood urea nitrogen, uric acid, lactate dehydrogenase, creatinine, chloride, bicarbonate, glucose, total protein, albumin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), phosphorous, and magnesium.

Complete blood count (CBC) with differential included hemoglobin, hematocrit, white blood cell (WBC) count with complete manual or automated differential (total neutrophils, lymphocytes, monocytes, eosinophils, basophils; reported as absolute counts), red blood cell (RBC) count, and platelet count.

Participants who received at least 1 dose of any study drug

Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

Participants with adequate oprozomib plasma concentration-versus-time data to allow estimation of pharmacokinetic (PK) parameters. Treatment groups receiving the same dose of oprozomib were combined for PK analyses.

Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

The area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method.

Participants with adequate oprozomib plasma concentration-versus-time data to allow estimation of pharmacokinetic (PK) parameters. Treatment groups receiving the same dose of oprozomib were combined for PK analyses.

Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

The area under the plasma concentration-time curve from time 0 to time infinity (AUCinf), estimated as the sum of AUClast and Clast/λz, where Clast is the last predicted concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase.

Participants with adequate oprozomib plasma concentration-versus-time data to allow estimation of pharmacokinetic (PK) parameters. Treatment groups receiving the same dose of oprozomib were combined for PK analyses.