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

• ClinicalTrials.gov Identifier: NCT02978235
• Recruitment Status: Terminated
• First Posted: November 30, 2016
• Last Update Posted: June 21, 2021
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; NonHodgkin Lymphoma	Drug: TAS4464	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label Safety, Pharmacokinetic and Efficacy Study of TAS4464 in Patients With Multiple Myeloma or Lymphoma
• Actual Study Start Date: March 1, 2017
• Actual Primary Completion Date: February 1, 2018
• Actual Study Completion Date: February 1, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: TAS4464	Drug: TAS4464; Intravenous (IV) Infusion

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Completion of Cycle 1 (28 days) ]
2. 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 [ Time Frame: Up to 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Provide written informed consent
2. 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:

1. Any of the following treatments, within the specified time frame, prior to the first dose of TAS4464:

   1. Major surgery within 28 days
   2. Radiation/chemotherapy within 21 days
   3. Monoclonal antibodies within 28 days
   4. Corticosteroid administration >20 mg/day of prednisone or equivalent within 14 days
   5. Proteasome inhibitors within 14 days
   6. Immunomodulatory agents within 7 days
   7. Stem cell transplant within 3 months
   8. Current immunosuppressive treatment for graft versus host disease
   9. Current use of an investigational agent
2. Active graft versus host disease
3. Known serious illness or medical condition
4. Prior treatment with TAS4464 or known hypersensitivity to any of its inactive ingredients or drugs similar in class
5. Pregnant or breast-feeding female

Contacts and Locations

Locations

United States, Maryland

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States, 48334

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New Jersey

John Theurer Cancer Center at Hackensack Meridian Health

Hackensack, New Jersey, United States, 07601

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

Sponsors and Collaborators

Taiho Oncology, Inc.

More Information

• Responsible Party: Taiho Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02978235
• Other Study ID Numbers: TAS-4464-101
• First Posted: November 30, 2016
• Last Update Posted: June 21, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Taiho Oncology, Inc.:

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

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders