A Dose Finding Study Followed by a Safety and Efficacy Study for Patients With Multiple Myeloma or Lymphoma

Study Overview
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Brief Summary
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The Phase 1 portion of this study will determine the safety of TAS4464 and the most appropriate dose for patients with Multiple Myeloma or Lymphoma.

Detailed Description
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The trial was put on Clinical Hold prior to Phase 2 due to cases of drug induced liver injury meeting the criteria for Hy's Law. Background and Rationale: • TAS4464 is an investigational NEDD8 activating enzyme (NAE) inhibitor, a compound which may affect cancer cell growth and survival. Thus, TAS4464 may help in the treatment of cancer. Phase 1: Primary: To investigate the safety and tolerability of TAS4464 To identify a tolerated dose of TAS4464 Secondary: To investigate the preliminary efficacy of TAS4464 To investigate the pharmacokinetics (PK) and the pharmacogenomics (PGx) of TAS4464 To investigate the pharmacodynamics of TAS4464

Official Title
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A Phase 1, Open-Label Safety, Pharmacokinetic and Efficacy Study of TAS4464 in Patients With Multiple Myeloma or Lymphoma

Conditions
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Multiple Myeloma, NonHodgkin Lymphoma

Intervention / Treatment
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* Drug: TAS4464


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Women of child-bearing potential must have a negative pregnancy test Multiple Myeloma: Confirmed diagnosis of Multiple Myeloma with measurable disease, having been treated with at least two prior lines of therapy. Lymphoma: Confirmed diagnosis of Non-Hodgkin Lymphoma with measurable disease, having been treated with at least one anthracycline-based therapy, with relapse or progression since the last treatment received. Exclusion Criteria: Any of the following treatments, within the specified time frame, prior to the first dose of TAS4464: Major surgery within 28 days Radiation/chemotherapy within 21 days Monoclonal antibodies within 28 days Corticosteroid administration >20 mg/day of prednisone or equivalent within 14 days Proteasome inhibitors within 14 days Immunomodulatory agents within 7 days Stem cell transplant within 3 months Current immunosuppressive treatment for graft versus host disease Current use of an investigational agent Active graft versus host disease Known serious illness or medical condition Prior treatment with TAS4464 or known hypersensitivity to any of its inactive ingredients or drugs similar in class Pregnant or breast-feeding female

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS4464<br> | Drug: TAS4464<br>* Intravenous (IV) Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing any dose-limiting toxicities, during dose escalation period, to determine maximum tolerated dose of TAS4464, using NCI CTCAE criteria, laboratory testing, performance status assessments, and other routine visit procedures |  | Completion of Cycle 1 (28 days) | 
| Efficacy of TAS4464, defined as Objective Response Rate (ORR) per IWG criteria (NHL) and IMWG criteria (MM). This will take into consideration routine assessments including: imaging scans, physical exams, blood tests, urine tests and biopsy results |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Relapsed/Refractory, Lymphoma, Non-Hodgkin Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, Mantle Cell Lymphoma, MCL, Peripheral T-Cell Lymphoma, PTCL, TAS4464, NEDD8, NAE inhibitor, Neoplasms, Hematologic Diseases, Myeloma