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

Study Overview
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Brief Summary
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A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in patients with relapsed refractory multiple myeloma.

Detailed Description
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A multicenter, non-randomized, open-label, dose-exploration study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in patients 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.

Official Title
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(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

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Immediate Release (IR) Formulation
* Drug: Gastro-Retentive (GR) Formulation
* Drug: Dexamethasone
* Drug: Pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subject must have a pathologically documented, definitively diagnosed, multiple myeloma relapsed, 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. Subject 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 Exclusion Criteria 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. POEMs syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). Plasma cell leukemia (> 2.0 X109/L circulating plasma cells by standard differential). Waldenstrom's macroglobulinemia. Other Exclusion Criteria May Apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Arm 1<br>Oprozomib (Immediate Release) plus dexamethasone | Drug: Immediate Release (IR) Formulation<br>* Immediate Release (IR) Formulation<br>Drug: Dexamethasone<br>* Dexamethasone<br>|
| Experimental: Part 1 Arm 2<br>Oprozomib (Gastro-retentive) plus dexamethasone | Drug: Gastro-Retentive (GR) Formulation<br>* Gastro-Retentive (GR) Formulation<br>Drug: Dexamethasone<br>* Dexamethasone<br>|
| Experimental: Part 2 Arm 1<br>Oprozomib (Immediate release) plus pomalidomide and dexamethasone | Drug: Immediate Release (IR) Formulation<br>* Immediate Release (IR) Formulation<br>Drug: Dexamethasone<br>* Dexamethasone<br>Drug: Pomalidomide<br>* Pomalidomide<br>|
| Experimental: Part 2 Arm 2<br>Oprozomib (Gastro-retentive) plus pomalidomide and dexamethasone | Drug: Gastro-Retentive (GR) Formulation<br>* Gastro-Retentive (GR) Formulation<br>Drug: Dexamethasone<br>* Dexamethasone<br>Drug: Pomalidomide<br>* Pomalidomide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose for each formulation of oprozomib in combination with pomalidomide and dexamethasone |  | The primary analysis will be based on subject data collected up to 2 months from the date of last subject enrollment | 
| Incidence of treatment-related adverse events for all subjects on continued oprozomib treatment |  | Data collected up to 2 months from the date of last subject enrollment. | 
| Incidence of treatment-emergent adverse events |  | Data collected up to 2 months from the date of last subject enrollment. | 
| Number of patients with changes in laboratory test results |  | The primary analysis will be based on subject data collected up to 2 months from the date of last subject enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) |  | At the highest concentration of drug in the blood. | 
| Time to Cmax (tmax) |  | time to achieve Cmax. | 
| Area under the concentration-time curve |  | time 0 to the time of last quantifiable concentration (AUClast) | 
| Overall response |  | All efficacy assessments will follow IMWG uniform response criteria and be performed every 4 weeks (± 1 week). | 
| Best overall response |  | All efficacy assessments will follow IMWG uniform response criteria and be performed every 4 weeks (± 1 week). | 
| Progression free survival |  | 4 months | 
| Duration of response |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma