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

Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01999335
Collaborator
(none)
33
Enrollment
17
Locations
5
Arms
56.8
Actual Duration (Months)
1.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the Phase 1 part of the study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of oprozomib in combination with pomalidomide and dexamethasone in adults with primary refractory or relapsed and refractory multiple myeloma.

The purpose of the Phase 3 part of the study is to compare the efficacy for adults with primary refractory or relapsed and refractory multiple myeloma who are randomized to either oprozomib or placebo in combination with pomalidomide and dexamethasone.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This was a phase 1b/3, multicenter study composed of 2 parts: part 1 was a phase 1b, open-label, dose-escalation and dose-expansion component and part 2 was to have been a phase 3, placebo-controlled, double-blind, randomized component. Part 2 was not conducted.

The Phase 1 dose-escalation portion of the study followed a standard 3 + 3 dose-escalation design. For each of the 2 schedules, groups of 3 to 6 patients were enrolled. The starting doses of oprozomib were 150 and 210 mg in the 5/14 and 2/7 schedules, respectively. The starting dose of pomalidomide was 4 mg in both schedules. As long as < 33% of patients experienced a dose-limiting toxicity (DLT) in a given cohort, the dose of oprozomib was escalated in 30-mg increments for successive cohorts.

Once the recommended dose and schedule for the expansion phase had been selected, additional participants were enrolled in the dose expansion portion of part 1 to continue the evaluation of the safety and efficacy of the regimen and determine the recommended phase 3 dose. Enrollment was halted during the dose expansion phase and part 2 was not conducted.

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b/3 Multicenter Study of Oprozomib, Pomalidomide, and Dexamethasone in Primary Refractory or Relapsed and Refractory Multiple Myeloma Subjects
Actual Study Start Date :
Jul 30, 2014
Actual Primary Completion Date :
Apr 25, 2019
Actual Study Completion Date :
Apr 25, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone

Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Drug: Oprozomib
Extended release (ER) tablets administered orally

Drug: Pomalidomide
Capsules for oral administration
Other Names:
  • POMALYST®

    • Drug: Dexamethasone
    Tablets for oral administration
    Experimental: Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone

    Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

    Drug: Oprozomib
    Extended release (ER) tablets administered orally

    Drug: Pomalidomide
    Capsules for oral administration
    Other Names:
  • POMALYST®

    • Drug: Dexamethasone
    Tablets for oral administration
    Experimental: Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone

    Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

    Drug: Oprozomib
    Extended release (ER) tablets administered orally

    Drug: Pomalidomide
    Capsules for oral administration
    Other Names:
  • POMALYST®

    • Drug: Dexamethasone
    Tablets for oral administration
    Experimental: Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone

    Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

    Drug: Oprozomib
    Extended release (ER) tablets administered orally

    Drug: Pomalidomide
    Capsules for oral administration
    Other Names:
  • POMALYST®

    • Drug: Dexamethasone
    Tablets for oral administration
    Experimental: Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase

    Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

    Drug: Oprozomib
    Extended release (ER) tablets administered orally

    Drug: Pomalidomide
    Capsules for oral administration
    Other Names:
  • POMALYST®

    • Drug: Dexamethasone
    Tablets for oral administration

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose-limiting Toxicities (DLTs) [Cycle 1, 28 days]

      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.

    2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [From first dose of any study drug up to 30 days after the last dose; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.]

      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.

    3. Number of Participants With Post-Baseline Grade 3 or 4 Laboratory Toxicities [Cycles 1 and 2 days 1, 5, 15, and 19 and days 3 and 8 of cycle 1, and day 1 of each cycle from cycle 3 thereafter until the end of treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.]

      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.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.]

      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.

    2. Clinical Benefit Rate (CBR) [Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.]

      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)

    3. Maximum Plasma Concentration (Cmax) of Oprozomib [Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.]

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

    4. Time to Maximum Plasma Concentration (Tmax) of Oprozomib [Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.]

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

    5. Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of Oprozomib [Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.]

      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.

    6. Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib [Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

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

    2. ≥ 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination)

    3. In the dose-expansion and Phase 3 portions of the study only: In addition to the above, treatment with adequate alkylator therapy, defined as:

    1. 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

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

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

    3. Serum M-protein ≥ 500 mg/dL

    4. Urine M-protein ≥ 200 mg/24 h

    5. 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

    6. Males and females ≥ 18 years old

    7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

    Key Exclusion Criteria:

    1. 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

    2. 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.

    3. Radiation therapy within 3 weeks before first dose. Radioimmunotherapy within 8 weeks before first dose.

    4. 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

    5. 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).

    6. Known hypersensitivity to any immunomodulatory drugs (IMiDs), including Grade 4 rash

    7. Prior treatment of any duration with pomalidomide

    8. Known hypersensitivity or intolerance to dexamethasone

    9. Prior exposure to oprozomib

    10. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 California Cancer Associates For Research and Exellence, cCare Encinitas California United States
    2 James R. Berenson, MD, Inc. West Hollywood California United States
    3 Innovative Clinical Research Institute Whittier California United States
    4 Rocky Mountain Cancer Centers Denver Colorado United States
    5 Oncology Hematology West PC, dba Nebraska Cancer Specialists Omaha Nebraska United States
    6 Weill Cornell Medical College-New York Presbyterian Hospital New York New York United States
    7 Levine Cancer Institute Charlotte North Carolina United States
    8 Duke University Medical Center Durham North Carolina United States
    9 Willamette Valley Cancer Institute and Research Center Springfield Oregon United States
    10 Abramson Cancer Center of the University of Pennsylvania at Perelman Center for Advanced Medicine Philadelphia Pennsylvania United States
    11 University of Pennsylvania Philadelphia Pennsylvania United States
    12 Tennessee Oncology, PLLC / Sarah Cannon Research Institute Nashville Tennessee United States
    13 The University of Texas M.D. Anderson Cancer Center Houston Texas United States
    14 Cancer Care Centers of South Texas-HOAST San Antonio Texas United States
    15 Virginia Cancer Specialists, PC Fairfax Virginia United States
    16 Virginia Oncology Associates Norfolk Virginia United States
    17 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01999335
    Other Study ID Numbers:
    • OPZ007
    • 20130411
    First Posted:
    Dec 3, 2013
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Mar 1, 2021
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Pomalidomide

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 12 centers in the United States. This study was composed of 2 parts: part 1 was a phase 1b, open-label, dose-escalation and dose-expansion component and part 2 was to have been a phase 3, placebo-controlled, double-blind, randomized component. Part 2 was not conducted.
    Pre-assignment Detail In part 1 participants were enrolled sequentially using a standard 3 + 3 dose escalation schema. Additional participants were to be enrolled in the dose expansion portion once the recommended dose and schedule had been selected; enrollment was halted after 12 participants were enrolled in the expansion cohort.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED 3 1 7 10 12
    Received Study Treatment 3 1 7 10 10
    COMPLETED 3 1 7 10 10
    NOT COMPLETED 0 0 0 0 2

    Baseline Characteristics

    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase Total
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 3 1 7 10 10 31
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.7
    (5.5)
    59.0
    57.1
    (12.9)
    68.2
    (7.3)
    63.7
    (6.0)
    62.6
    (9.3)
    Sex: Female, Male (Count of Participants)
    Female
    3
    100%
    0
    0%
    3
    42.9%
    2
    20%
    5
    50%
    13
    41.9%
    Male
    0
    0%
    1
    100%
    4
    57.1%
    8
    80%
    5
    50%
    18
    58.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    2
    28.6%
    1
    10%
    0
    0%
    3
    9.7%
    Not Hispanic or Latino
    3
    100%
    1
    100%
    4
    57.1%
    8
    80%
    8
    80%
    24
    77.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    14.3%
    1
    10%
    2
    20%
    4
    12.9%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black
    1
    33.3%
    0
    0%
    2
    28.6%
    4
    40%
    1
    10%
    8
    25.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    2
    66.7%
    1
    100%
    4
    57.1%
    6
    60%
    7
    70%
    20
    64.5%
    Not reported
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    2
    20%
    3
    9.7%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    Grade 0 (Fully active)
    0
    0%
    0
    0%
    2
    28.6%
    4
    40%
    3
    30%
    9
    29%
    Grade 1 (Restricted but ambulatory)
    3
    100%
    1
    100%
    5
    71.4%
    4
    40%
    6
    60%
    19
    61.3%
    Grade 2 (Ambulatory but unable to work)
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    1
    10%
    3
    9.7%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Dose-limiting Toxicities (DLTs)
    Description 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.
    Time Frame Cycle 1, 28 days

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of any study drug
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 1 7 10 10
    Any dose-limiting toxicity
    2
    66.7%
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    Gastric hemorrhage
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    Abdominal distension
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cognitive disorder
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Mucosal inflammation
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
    Description 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.
    Time Frame From first dose of any study drug up to 30 days after the last dose; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of any study drug
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 1 7 10 10
    Any treatment-emergent adverse event
    3
    100%
    1
    100%
    7
    100%
    10
    100%
    10
    100%
    TEAE Grade ≥ 3
    2
    66.7%
    1
    100%
    5
    71.4%
    9
    90%
    9
    90%
    Serious adverse events
    0
    0%
    1
    100%
    3
    42.9%
    6
    60%
    6
    60%
    TEAEs leading to discontinuation of study drug
    1
    33.3%
    0
    0%
    2
    28.6%
    1
    10%
    4
    40%
    Fatal adverse events
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Treatment-related treatment-emergent adverse events (TRAE)
    3
    100%
    1
    100%
    7
    100%
    10
    100%
    10
    100%
    Treatment-related TEAE Grade ≥ 3
    2
    66.7%
    1
    100%
    4
    57.1%
    6
    60%
    7
    70%
    Treatment-related serious adverse events
    0
    0%
    0
    0%
    1
    14.3%
    2
    20%
    2
    20%
    TRAEs leading to discontinuation of study drug
    1
    33.3%
    0
    0%
    1
    14.3%
    1
    10%
    4
    40%
    Treatment-related fatal adverse events
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description 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.
    Time Frame Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of any study drug
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 1 7 10 10
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    1110%
    100.0
    10000%
    85.7
    1224.3%
    60.0
    600%
    60.0
    600%
    4. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description 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)
    Time Frame Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of any study drug
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 1 7 10 10
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    1110%
    100.0
    10000%
    85.7
    1224.3%
    60.0
    600%
    60.0
    600%
    5. Secondary Outcome
    Title Maximum Plasma Concentration (Cmax) of Oprozomib
    Description Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.
    Time Frame Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 or 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 16 9
    Cycle 1 day 1
    492
    (398.3)
    744
    (119.4)
    757
    (38.7)
    Cycle 2 day 1
    181
    (401.1)
    1030
    (91.5)
    965
    (44.4)
    6. Primary Outcome
    Title Number of Participants With Post-Baseline Grade 3 or 4 Laboratory Toxicities
    Description 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.
    Time Frame Cycles 1 and 2 days 1, 5, 15, and 19 and days 3 and 8 of cycle 1, and day 1 of each cycle from cycle 3 thereafter until the end of treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of any study drug
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 1 7 10 10
    At least 1 Grade 3 or 4 laboratory toxicity
    2
    66.7%
    1
    100%
    6
    85.7%
    8
    80%
    8
    80%
    Grade 3 increase in glucose
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    1
    10%
    Grade 4 increase in glucose
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    Grade 3 increase in total bilirubin
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    Grade 3 increase in magnesium
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    Grade 4 decrease in magnesium
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    Grade 3 decrease in sodium
    0
    0%
    0
    0%
    0
    0%
    3
    30%
    0
    0%
    Grade 4 decrease in sodium
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    Grade 3 decrease in hemoglobin
    1
    33.3%
    1
    100%
    2
    28.6%
    1
    10%
    3
    30%
    Grade 3 decrease in leukocytes
    1
    33.3%
    1
    100%
    1
    14.3%
    1
    10%
    2
    20%
    Grade 4 decrease in leukocytes
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    Grade 3 decrease in neutrophils
    2
    66.7%
    1
    100%
    3
    42.9%
    1
    10%
    4
    40%
    Grade 4 decrease in neutrophils
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    Grade 3 decrease in lymphocytes
    1
    33.3%
    0
    0%
    5
    71.4%
    3
    30%
    4
    40%
    Grade 4 decrease in lymphocytes
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    0
    0%
    Grade 3 decrease in platelets
    1
    33.3%
    0
    0%
    0
    0%
    2
    20%
    5
    50%
    7. Secondary Outcome
    Title Time to Maximum Plasma Concentration (Tmax) of Oprozomib
    Description Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.
    Time Frame Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 or 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 16 9
    Cycle 1 day 1
    1.0
    1.6
    2.2
    Cycle 2 day 1
    4.0
    1.1
    1.1
    8. Secondary Outcome
    Title Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of Oprozomib
    Description 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.
    Time Frame Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 or 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 3 16 9
    Cycle 1 day 1
    1090
    (192.2)
    1700
    (145.9)
    1730
    (48.7)
    Cycle 2 day 1
    446
    (605.7)
    1860
    (81.9)
    1800
    (17.2)
    9. Secondary Outcome
    Title Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib
    Description 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.
    Time Frame Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 or 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    Measure Participants 2 8 5
    Cycle 1 day 1
    2250
    (NA)
    3440
    (96.1)
    1660
    (35.8)
    Cycle 2 day 1
    1830
    (87.7)
    1900
    (12.4)

    Adverse Events

    Time Frame All-cause mortality: From the date of enrollment until the data cutoff of 25 April 2019, a maximum of 51 months. Treatment-emergent adverse events: From the first dose of any study treatment and within the end of study or 30 days of the last dose of any study treatment, whichever occurred earlier; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
    Adverse Event Reporting Description All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of any study drug.
    Arm/Group Title Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Arm/Group Description Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity. Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.
    All Cause Mortality
    Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 0/1 (0%) 4/7 (57.1%) 3/10 (30%) 4/12 (33.3%)
    Serious Adverse Events
    Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 1/1 (100%) 3/7 (42.9%) 6/10 (60%) 6/10 (60%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 3/10 (30%)
    Cardiac disorders
    CARDIAC FAILURE CONGESTIVE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    SUPRAVENTRICULAR TACHYCARDIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Gastrointestinal disorders
    GASTRIC HAEMORRHAGE 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    General disorders
    PYREXIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Infections and infestations
    ABSCESS JAW 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    CELLULITIS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    INFLUENZA 0/3 (0%) 1/1 (100%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    ORAL INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PARAINFLUENZAE VIRUS INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PLEURAL INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PNEUMONIA 0/3 (0%) 1/1 (100%) 0/7 (0%) 2/10 (20%) 2/10 (20%)
    PNEUMONIA VIRAL 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    SEPSIS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    SINUSITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    VIRAL INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Injury, poisoning and procedural complications
    FEMORAL NECK FRACTURE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    RIB FRACTURE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Investigations
    NEUTROPHIL COUNT DECREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 0/3 (0%) 1/1 (100%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    Nervous system disorders
    COGNITIVE DISORDER 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    HAEMOTHORAX 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PNEUMONITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PULMONARY EMBOLISM 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PULMONARY OEDEMA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Vascular disorders
    DEEP VEIN THROMBOSIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Other (Not Including Serious) Adverse Events
    Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 1/1 (100%) 7/7 (100%) 10/10 (100%) 10/10 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 1/3 (33.3%) 1/1 (100%) 3/7 (42.9%) 4/10 (40%) 7/10 (70%)
    HYPERCOAGULATION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    INCREASED TENDENCY TO BRUISE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    LEUKOCYTOSIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    LEUKOPENIA 0/3 (0%) 1/1 (100%) 1/7 (14.3%) 1/10 (10%) 3/10 (30%)
    NEUTROPENIA 0/3 (0%) 1/1 (100%) 3/7 (42.9%) 2/10 (20%) 3/10 (30%)
    THROMBOCYTOPENIA 1/3 (33.3%) 1/1 (100%) 1/7 (14.3%) 1/10 (10%) 6/10 (60%)
    Cardiac disorders
    ATRIAL FIBRILLATION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PALPITATIONS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    SUPRAVENTRICULAR TACHYCARDIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    TACHYCARDIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Ear and labyrinth disorders
    TINNITUS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    VERTIGO 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 2/10 (20%)
    Eye disorders
    CATARACT 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    DRY EYE 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 2/10 (20%)
    EYE HAEMATOMA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    EYE IRRITATION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    LACRIMATION INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PERIORBITAL OEDEMA 0/3 (0%) 1/1 (100%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    SCLERAL HAEMORRHAGE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    VISION BLURRED 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 2/10 (20%)
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 1/3 (33.3%) 0/1 (0%) 2/7 (28.6%) 4/10 (40%) 0/10 (0%)
    ABDOMINAL PAIN 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    ABDOMINAL PAIN UPPER 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 2/10 (20%)
    CONSTIPATION 2/3 (66.7%) 0/1 (0%) 3/7 (42.9%) 6/10 (60%) 6/10 (60%)
    DENTAL DISCOMFORT 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    DIARRHOEA 2/3 (66.7%) 0/1 (0%) 7/7 (100%) 9/10 (90%) 8/10 (80%)
    DIVERTICULAR PERFORATION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    DYSPEPSIA 1/3 (33.3%) 0/1 (0%) 3/7 (42.9%) 3/10 (30%) 3/10 (30%)
    ERUCTATION 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    FLATULENCE 1/3 (33.3%) 0/1 (0%) 2/7 (28.6%) 3/10 (30%) 0/10 (0%)
    FREQUENT BOWEL MOVEMENTS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    GASTROINTESTINAL PAIN 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 0/10 (0%) 0/10 (0%)
    GASTROOESOPHAGEAL REFLUX DISEASE 0/3 (0%) 0/1 (0%) 0/7 (0%) 3/10 (30%) 1/10 (10%)
    GINGIVAL PAIN 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    HYPOAESTHESIA ORAL 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    NAUSEA 1/3 (33.3%) 1/1 (100%) 5/7 (71.4%) 10/10 (100%) 5/10 (50%)
    OESOPHAGEAL PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    STOMATITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    TOOTH LOSS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    VOMITING 2/3 (66.7%) 1/1 (100%) 4/7 (57.1%) 8/10 (80%) 6/10 (60%)
    General disorders
    ASTHENIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 3/10 (30%)
    CHEST PAIN 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 1/10 (10%)
    CHILLS 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 1/10 (10%) 3/10 (30%)
    FACE OEDEMA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    FATIGUE 0/3 (0%) 0/1 (0%) 6/7 (85.7%) 7/10 (70%) 8/10 (80%)
    GAIT DISTURBANCE 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 0/10 (0%)
    INFLUENZA LIKE ILLNESS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 1/10 (10%)
    MALAISE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    MUCOSAL INFLAMMATION 2/3 (66.7%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    NON-CARDIAC CHEST PAIN 0/3 (0%) 1/1 (100%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    OEDEMA 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 1/10 (10%) 1/10 (10%)
    OEDEMA PERIPHERAL 0/3 (0%) 1/1 (100%) 2/7 (28.6%) 2/10 (20%) 1/10 (10%)
    PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PYREXIA 1/3 (33.3%) 1/1 (100%) 2/7 (28.6%) 2/10 (20%) 3/10 (30%)
    SWELLING 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Infections and infestations
    BRONCHITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    CANDIDA INFECTION 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    CELLULITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    CONJUNCTIVITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    CYSTITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    DIVERTICULITIS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    EYE INFECTION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    FUNGAL INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    LUNG INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    NASOPHARYNGITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    ORAL CANDIDIASIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 3/10 (30%) 1/10 (10%)
    PAROTITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PNEUMONIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    SALMONELLOSIS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    SEPSIS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    SINUSITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 0/10 (0%)
    UPPER RESPIRATORY TRACT INFECTION 2/3 (66.7%) 0/1 (0%) 4/7 (57.1%) 4/10 (40%) 2/10 (20%)
    URINARY TRACT INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    VIRAL INFECTION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    VIRAL UPPER RESPIRATORY TRACT INFECTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 0/10 (0%)
    Injury, poisoning and procedural complications
    CONTUSION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 2/10 (20%)
    FALL 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 1/10 (10%) 2/10 (20%)
    LACERATION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    ROAD TRAFFIC ACCIDENT 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    SKIN ABRASION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    TOXICITY TO VARIOUS AGENTS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    WOUND 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    ASPARTATE AMINOTRANSFERASE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    ASPARTATE AMINOTRANSFERASE INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 2/10 (20%)
    BLOOD ALKALINE PHOSPHATASE INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 2/10 (20%)
    BLOOD BILIRUBIN INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    BLOOD CREATININE INCREASED 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 2/10 (20%) 3/10 (30%)
    BLOOD LACTATE DEHYDROGENASE INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    BLOOD LACTIC ACID INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    BLOOD THYROID STIMULATING HORMONE INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    ELECTROCARDIOGRAM QT PROLONGED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 0/10 (0%)
    GLOMERULAR FILTRATION RATE DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    INTERNATIONAL NORMALISED RATIO DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    INTERNATIONAL NORMALISED RATIO INCREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    LYMPHOCYTE COUNT DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    NEUTROPHIL COUNT DECREASED 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 2/10 (20%) 4/10 (40%)
    NEUTROPHIL COUNT INCREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    PLATELET COUNT DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 3/10 (30%) 1/10 (10%)
    PROTEIN TOTAL DECREASED 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    WEIGHT DECREASED 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    WHITE BLOOD CELL COUNT DECREASED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 4/10 (40%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 1/3 (33.3%) 0/1 (0%) 1/7 (14.3%) 3/10 (30%) 1/10 (10%)
    DEHYDRATION 0/3 (0%) 1/1 (100%) 2/7 (28.6%) 2/10 (20%) 0/10 (0%)
    HYPERCALCAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    HYPERCHLORAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    HYPERGLYCAEMIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 3/10 (30%)
    HYPERKALAEMIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 3/10 (30%)
    HYPERMAGNESAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    HYPERPHOSPHATAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 2/10 (20%)
    HYPERURICAEMIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 2/10 (20%)
    HYPOALBUMINAEMIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 3/10 (30%)
    HYPOCALCAEMIA 0/3 (0%) 1/1 (100%) 0/7 (0%) 2/10 (20%) 3/10 (30%)
    HYPOGLYCAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    HYPOKALAEMIA 0/3 (0%) 1/1 (100%) 2/7 (28.6%) 3/10 (30%) 2/10 (20%)
    HYPOMAGNESAEMIA 0/3 (0%) 1/1 (100%) 2/7 (28.6%) 4/10 (40%) 5/10 (50%)
    HYPONATRAEMIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 2/10 (20%)
    HYPOPHOSPHATAEMIA 0/3 (0%) 0/1 (0%) 3/7 (42.9%) 1/10 (10%) 2/10 (20%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 2/10 (20%)
    BACK PAIN 1/3 (33.3%) 1/1 (100%) 3/7 (42.9%) 2/10 (20%) 1/10 (10%)
    BONE PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    JAW DISORDER 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    JOINT SWELLING 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    MUSCLE SPASMS 0/3 (0%) 1/1 (100%) 1/7 (14.3%) 1/10 (10%) 1/10 (10%)
    MUSCULAR WEAKNESS 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 1/10 (10%) 0/10 (0%)
    MUSCULOSKELETAL CHEST PAIN 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    MUSCULOSKELETAL PAIN 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 0/10 (0%)
    MYALGIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 2/10 (20%)
    NECK PAIN 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    PAIN IN EXTREMITY 1/3 (33.3%) 0/1 (0%) 3/7 (42.9%) 0/10 (0%) 1/10 (10%)
    PAIN IN JAW 2/3 (66.7%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    MELANOCYTIC NAEVUS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Nervous system disorders
    AMNESIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    APHASIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    COGNITIVE DISORDER 1/3 (33.3%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    DEMENTIA ALZHEIMER'S TYPE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    DEPRESSED LEVEL OF CONSCIOUSNESS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    DIZZINESS 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 2/10 (20%) 4/10 (40%)
    DYSGEUSIA 1/3 (33.3%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    HEADACHE 0/3 (0%) 0/1 (0%) 0/7 (0%) 3/10 (30%) 4/10 (40%)
    HYPERSOMNIA 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    HYPOAESTHESIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    MEMORY IMPAIRMENT 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    NEURALGIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    NEUROPATHY PERIPHERAL 0/3 (0%) 0/1 (0%) 0/7 (0%) 4/10 (40%) 1/10 (10%)
    PERIPHERAL SENSORY NEUROPATHY 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 1/10 (10%)
    SEIZURE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    SOMNOLENCE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    SYNCOPE 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    TREMOR 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Psychiatric disorders
    AGITATION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    ANXIETY 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 2/10 (20%) 0/10 (0%)
    CONFUSIONAL STATE 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    INSOMNIA 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 2/10 (20%) 4/10 (40%)
    MOOD ALTERED 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    MOOD SWINGS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    RESTLESSNESS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 2/10 (20%) 0/10 (0%)
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    DYSURIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    HAEMATURIA 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    URINARY RETENTION 0/3 (0%) 1/1 (100%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    Reproductive system and breast disorders
    PELVIC PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 0/3 (0%) 0/1 (0%) 3/7 (42.9%) 3/10 (30%) 2/10 (20%)
    DYSPHONIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    DYSPNOEA 0/3 (0%) 1/1 (100%) 1/7 (14.3%) 2/10 (20%) 3/10 (30%)
    DYSPNOEA EXERTIONAL 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    EPISTAXIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 0/10 (0%)
    HICCUPS 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 0/10 (0%)
    HYPERCAPNIA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    NASAL CONGESTION 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 3/10 (30%) 0/10 (0%)
    OROPHARYNGEAL PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 3/10 (30%) 3/10 (30%)
    PLEURAL EFFUSION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    PRODUCTIVE COUGH 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 1/10 (10%) 0/10 (0%)
    PULMONARY HYPERTENSION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    RESPIRATORY TRACT CONGESTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    RHINITIS ALLERGIC 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    RHINORRHOEA 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 3/10 (30%)
    SINUS CONGESTION 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 0/10 (0%)
    SINUS PAIN 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    SNEEZING 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    UPPER-AIRWAY COUGH SYNDROME 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    WHEEZING 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 1/10 (10%)
    Skin and subcutaneous tissue disorders
    BLISTER 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    DERMATITIS CONTACT 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    ERYTHEMA 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    HYPERHIDROSIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 2/10 (20%) 1/10 (10%)
    NIGHT SWEATS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    PRURITUS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 1/10 (10%)
    RASH 1/3 (33.3%) 1/1 (100%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    RASH PRURITIC 1/3 (33.3%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 0/10 (0%)
    SKIN ULCER 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    Vascular disorders
    DEEP VEIN THROMBOSIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    HOT FLUSH 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 1/10 (10%)
    HYPERTENSION 0/3 (0%) 0/1 (0%) 0/7 (0%) 0/10 (0%) 2/10 (20%)
    HYPOTENSION 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)
    ORTHOSTATIC HYPOTENSION 0/3 (0%) 0/1 (0%) 2/7 (28.6%) 0/10 (0%) 0/10 (0%)
    PHLEBITIS 0/3 (0%) 0/1 (0%) 0/7 (0%) 1/10 (10%) 0/10 (0%)
    VASCULAR RUPTURE 0/3 (0%) 0/1 (0%) 1/7 (14.3%) 0/10 (0%) 0/10 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email medinfo@amgen.com
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01999335
    Other Study ID Numbers:
    • OPZ007
    • 20130411
    First Posted:
    Dec 3, 2013
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Mar 1, 2021