Relapsed or Refractory Multiple MyelomaPhase 1INTREPID-1NCT02939183

Phase 1b Study Evaluating OPomD in Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing Immediate Release (IR) Formulation, Gastro-Retentive (GR) Formulation and Dexamethasone in people with Relapsed or Refractory Multiple Myeloma, run by Amgen at 20 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma. Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Relapsed or Refractory Multiple Myeloma
What is being tested?: Immediate Release (IR) Formulation, Gastro-Retentive (GR) Formulation and Dexamethasone
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 61 participants
Where: 20 sitesin 4 countries
Study dates: 17 Jan 2017to 6 Oct 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participant must have a pathologically documented, definitively diagnosed, multiple myeloma relapse, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide.
Participant must be willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
Measurable disease (assessed within 28 days prior to day 1).
Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
Other Inclusion Criteria May Apply

Who cannot join

Currently receiving treatment in another investigational device or drug study, or less than 28 days or 5 half-lives whichever is shorter since ending treatment on another investigational device or drug study(s).
Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following: received the transplant within 6 months prior to study day 1; received immunosuppressive therapy within the last 3 months prior to study day 1; having signs or symptoms of acute or chronic graft-versus-host disease.
Autologous stem cell transplant < 90 days prior to study day 1.
Multiple myeloma with IgM subtype.
POEM syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
Plasma cell leukemia (> 2.0 X10^9/L circulating plasma cells by standard differential).
Waldenstrom's macroglobulinemia.
Other Exclusion Criteria May Apply

Trial locations and contacts

20 sites in 4 countries.

Country

City, postcode or hospital

20 sites in 4 countries

United States13 sites

Research Site
Atlanta, Georgia, 30322
Research Site
Bethesda, Maryland, 20817
Research Site
Canton, Ohio, 44718
Research Site
Charlotte, North Carolina, 28204
Research Site
Chicago, Illinois, 60637-6613
Research Site
Cleveland, Ohio, 44195
Research Site
Hackensack, New Jersey, 07601
Research Site
Milwaukee, Wisconsin, 53226
Research Site
New York, New York, 10021
Research Site
San Antonio, Texas, 78229
Research Site
St Louis, Missouri, 63110
Research Site
Tampa, Florida, 33612
Research Site
West Hollywood, California, 90069

Other trials in United States

Australia3 sites

Research Site
Clayton, Victoria, 3168
Research Site
Murdoch, Western Australia, 6150
Research Site
Perth, Western Australia, 6000

Other trials in Australia

Canada2 sites

Research Site
Calgary, Alberta, T2N 2T9
Research Site
Toronto, Ontario, M5G 2C1

Other trials in Canada

Spain2 sites

Research Site
Pamplona, Navarre, 31008
Research Site
Salamanca, Castille and León, 37007

Other trials in Spain

About this study

Official title: (INTREPID-1) A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Oprozomib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.

Read the detailed description

A multicenter, non-randomized, open-label, dose-exploration study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma. The study will be conducted in two parts. Part 1 will evaluate the formulations of oprozomib in combination with dexamethasone only. Part 2 will evaluate the formulations of oprozomib administered at increasing dose levels (dose escalation) in combination with pomalidomide and dexamethasone.

Conditions: Relapsed or Refractory Multiple Myeloma
Being tested: Immediate Release (IR) Formulation, Gastro-Retentive (GR) Formulation, Dexamethasone, Pomalidomide
Keywords: Multiple Myeloma
Medical subject headings: Recurrence, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Immediate Release (IR) FormulationDrug
Immediate Release (IR) Formulation
Gastro-Retentive (GR) FormulationDrug
Gastro-Retentive (GR) Formulation
DexamethasoneDrug
Dexamethasone
PomalidomideDrug
Pomalidomide

Study groups in NCT02939183
Study group	Role	What they receive
Part 1 Oprozomib Immediate-release (IR) + Dexamethasone	Experimental	Oprozomib IR plus dexamethasone Receives: Drug: Immediate Release (IR) Formulation; Drug: Dexamethasone
Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone	Experimental	Oprozomib GR plus dexamethasone Receives: Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone	Experimental	Oprozomib IR plus pomalidomide and dexamethasone Receives: Drug: Immediate Release (IR) Formulation; Drug: Dexamethasone; Drug: Pomalidomide
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone	Experimental	Oprozomib GR plus pomalidomide and dexamethasone Receives: Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone; Drug: Pomalidomide
Open-label Roll-over	Experimental	Oprozomib GR monotherapy, or oprozomib GR plus dexamethasone Receives: Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia > 24 hours); Grade 3 nausea, vomiting and diarrhea < 3 days; Grade 3 fatigue < 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count < 0.5 x 10^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Measured: Day 1 to day 28 of cycle 1, where each cycle was 28 days
Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone
The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (>25% to 100%) is <40%.
DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia > 24 hours); Grade 3 nausea, vomiting and diarrhea < 3 days; Grade 3 fatigue < 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count < 0.5 x 10^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Measured: Day 1 to Day 28 of cycle 1, where each cycle was 28 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.
Measured: Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)
TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.
Measured: Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks

Secondary outcomes (8)

Maximum Observed Concentration (Cmax) of Oprozomib
The mean Cmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Measured: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Time to Cmax (Tmax) of Oprozomib
The median Tmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Measured: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib
The mean AUClast of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Measured: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
BOR was the best response per IMWG-URC from best to worst: stringent complete response (sCR; complete response [CR], normal serum free light chain ratio, no clonal cells in bone marrow [BM]), CR (negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in BM), very good partial response (VGPR; serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein [urine M-protein level < 100 mg/24-h]), partial response (PR; ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or < 200 mg/24-h), minimal response (MR; 25-49% reduction of serum M-protein and 50-89% in 24-h urinary M-protein, exceeding 200 mg/24-h), stable disease (SD; not CR, VGPR, PR or progressive disease [PD]), and PD (≥ 25% increase in serum or urine M-component, development of new or increased size of existing bone lesions or soft tissue plasmacytomas, hypercalcemia attributed to the plasma cell proliferative disorder).
Measured: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Overall Response Rate (ORR) According to IMWG-URC
The ORR was defined as the percentage of participants with a BOR of sCR, CR, VGPR, and PR per the IMWG-URC. Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to < 200 mg/24-h. The 95% confidence intervals (CIs) were estimated using the Clopper-Pearson method.
Measured: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Number of Participants With Progression Free Survival (PFS) Events
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. The number of participants who had a PFS event or who were censored are presented. PFS events were an assessment of progressive disease according to the IMWG-URC or death due to any cause. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
Measured: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of PFS
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. Median PFS was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
Measured: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of Duration of Response (DOR)
DOR, presented in months, was defined as the number of days between the date of the first tumor assessment indicating an objective response (PR or better) through to the subsequent date of progression or death due to any cause, or where applicable date of censoring (date of first progressive disease assessment or death or date of censoring - date of the first objective response result + 1/30.4). Median PFS was estimated using the Kaplan-Meier method. 95% confidence intervals were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Measured: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jan 20176 Oct 2022

First posted19 Oct 2016 (estimated)
Study start17 Jan 2017
Primary completion6 Oct 2022
Study completion6 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Relapsed or Refractory Multiple MyelomaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02939183
Sponsor's protocol ID: 20160104
Acronym: INTREPID-1
Status last verified: Sep 2024
First submitted: 18 Oct 2016
Last updated: 26 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Relapsed or Refractory Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: (INTREPID-1) A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Oprozomib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
ClinicalTrials.gov ID: NCT02939183
Acronym / sponsor ID: INTREPID-1 / 20160104
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Multiple Myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 17 Jan 2017 (actual)
Primary completion: 6 Oct 2022 (actual)
Study completion: 6 Oct 2022 (actual)
First posted: 19 Oct 2016 (estimated)
Results: Posted 26 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Part 1 Oprozomib Immediate-release (IR) + Dexamethasone	Experimental	Drug: Immediate Release (IR) Formulation, Drug: DexamethasoneOprozomib IR plus dexamethasone
Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone	Experimental	Drug: Gastro-Retentive (GR) Formulation, Drug: DexamethasoneOprozomib GR plus dexamethasone
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone	Experimental	Drug: Immediate Release (IR) Formulation, Drug: Dexamethasone, Drug: PomalidomideOprozomib IR plus pomalidomide and dexamethasone
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone	Experimental	Drug: Gastro-Retentive (GR) Formulation, Drug: Dexamethasone, Drug: PomalidomideOprozomib GR plus pomalidomide and dexamethasone
Open-label Roll-over	Experimental	Drug: Gastro-Retentive (GR) Formulation, Drug: DexamethasoneOprozomib GR monotherapy, or oprozomib GR plus dexamethasone

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Participant must have a pathologically documented, definitively diagnosed, multiple myeloma relapse, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide.
Participant must be willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
Measurable disease (assessed within 28 days prior to day 1).
Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
Other Inclusion Criteria May Apply

Key exclusion criteria (8 listed)

Currently receiving treatment in another investigational device or drug study, or less than 28 days or 5 half-lives whichever is shorter since ending treatment on another investigational device or drug study(s).
Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following: received the transplant within 6 months prior to study day 1; received immunosuppressive therapy within the last 3 months prior to study day 1; having signs or symptoms of acute or chronic graft-versus-host disease.
Autologous stem cell transplant < 90 days prior to study day 1.
Multiple myeloma with IgM subtype.
POEM syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Immediate Release (IR) FormulationImmediate Release (IR) Formulation	Drug	Part 1 Oprozomib Immediate-release (IR) + Dexamethasone, Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
Gastro-Retentive (GR) FormulationGastro-Retentive (GR) Formulation	Drug	Open-label Roll-over, Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone, Part 2 Oprozomib GR + Pomalidomide + Dexamethasone
DexamethasoneDexamethasone	Drug	Open-label Roll-over, Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone, Part 1 Oprozomib Immediate-release (IR) + Dexamethasone, Part 2 Oprozomib GR + Pomalidomide + Dexamethasone, Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
PomalidomidePomalidomide	Drug	Part 2 Oprozomib GR + Pomalidomide + Dexamethasone, Part 2 Oprozomib IR + Pomalidomide + Dexamethasone

Primary outcome

Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)
Time frame: Day 1 to day 28 of cycle 1, where each cycle was 28 days
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia > 24 hours); Grade 3 nausea, vomiting and diarrhea < 3 days; Grade 3 fatigue < 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count < 0.5 x 10^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone
Time frame: Day 1 to Day 28 of cycle 1, where each cycle was 28 days
The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (>25% to 100%) is <40%. DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia > 24 hours); Grade 3 nausea, vomiting and diarrhea < 3 days; Grade 3 fatigue < 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count < 0.5 x 10^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)
Time frame: Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.
Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)
Time frame: Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks
TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.

8 secondary outcomes

Maximum Observed Concentration (Cmax) of Oprozomib
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Time to Cmax (Tmax) of Oprozomib
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Overall Response Rate (ORR) According to IMWG-URC
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Number of Participants With Progression Free Survival (PFS) Events
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of PFS
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of Duration of Response (DOR)
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks

Results and safety

Results posted to the registry on 26 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Oprozomib IR 150 mg/Day + Dexamethsone	5	5
Oprozomib GR 150 mg/Day + Dexamethasone	8	5
Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone	3	2
Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone	5	2
Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone	9	7
Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone	5	3
Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone	11	4
Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone	8	5
Open-label Roll-over	7	1

Primary outcome: Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)

Time frame: Day 1 to day 28 of cycle 1, where each cycle was 28 days. Count of participants. Unit: Participants

Measure	Oprozomib IR 150 mg/Day + Dexamethsone n = 5	Oprozomib GR 150 mg/Day + Dexamethasone n = 8	Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone n = 4	Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone n = 4	Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone n = 8	Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone n = 5	Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone n = 10	Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone n = 8
Value	0	0	1	1	1	1	0	2

Population analysed: DLT-evaluable participants received the following during the 28-day DLT window: all planned doses of oprozomib, a minimum of 17 of 21 planned doses of pomalidomide, and a minimum of 6 of 8 planned doses of dexamethasone. One participant enrolled in arm Oprozomib IR 200 mg/day + pomalidomide + dexamethasone received oprozomib IR 150 mg + pomalidomide + dexamethasone, and this participant was included in the Oprozomib IR 150 mg + pomalidomide + dexamethasone arm.

Primary outcome: Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone

Time frame: Day 1 to Day 28 of cycle 1, where each cycle was 28 days. Number. Unit: mg/day

Measure	All Doses Oprozomib IR + Pomalidomide + Dexamethasone n = 30	All Doses Oprozomib GR + Pomalidomide + Dexamethasone n = 9
Value	250	NA

Population analysed: DLT-evaluable participants in Part 2 who received the following during the 28-day DLT window: all planned doses of oprozomib, a minimum of 17 of 21 planned doses of pomalidomide, and a minimum of 6 of 8 planned doses of dexamethasone.

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)

Time frame: Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks. Count of participants. Unit: Participants

Measure	Oprozomib IR 150 mg/Day + Dexamethsone n = 5	Oprozomib GR 150 mg/Day + Dexamethasone n = 8	Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone n = 4	Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone n = 4	Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone n = 8	Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone n = 5	Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone n = 10	Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone n = 8
Any TEAE	4	8	4	4	8	5	10	8
Any Treatment-related TEAE	4	8	4	4	8	5	10	8

Population analysed: Participants in the safety analysis set who received any amount of oprozomib, pomalidomide and/or dexamethasone in Parts 1 and 2.

Primary outcome: Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)

Time frame: Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks. Count of participants. Unit: Participants

Measure	Open-label Roll-over n = 7
Any TEAE	7
Any Serious TEAE	4

Population analysed: The safety analysis set for roll-over participants included all roll-over participants who received any amount of oprozomib, pomalidomide and/or dexamethasone. Participants enrolled in this study from other Amgen studies were included in a single roll-over arm, as pre-specified in the SAP.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events were collected from the first dose of study treatment until the last dose + 30 days; median treatment duration in Part 1 was 11.43 weeks, in Part 2 was 28 weeks, and in the open-label roll-over arm was 75.14 weeks. All-cause mortality was collected from enrollment to end of study visit; median overall duration on study was 259.00 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Oprozomib IR 150 mg/Day + Dexamethsone	2 of 5 (40%)	4 of 5 (80%)	0 of 5
Oprozomib GR 150 mg/Day + Dexamethasone	2 of 8 (25%)	8 of 8 (100%)	0 of 8
Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone	2 of 4 (50%)	4 of 4 (100%)	1 of 3
Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone	4 of 4 (100%)	4 of 4 (100%)	0 of 5
Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone	6 of 8 (75%)	8 of 8 (100%)	0 of 9
Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone	5 of 5 (100%)	5 of 5 (100%)	2 of 5
Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone	3 of 10 (30%)	10 of 10 (100%)	1 of 11
Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone	4 of 8 (50%)	8 of 8 (100%)	0 of 8
Open-label Roll-over	4 of 7 (57.1%)	7 of 7 (100%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

20 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Australia, Canada, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose-Limiting Toxcity (DLT) (time frame: Day 1 to day 28 of cycle 1, where each cycle was 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02939183.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2024; AzTrials last refreshed its copy on 27 Oct 2026.