A Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-079 Administered Subcutaneously as a Single Agent in Participants With Relapsed/Refractory (r/r) Multiple Myeloma (MM)

NCT03439280 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-079-1501U1111-1208-3202
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to assess the safety and tolerability, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of TAK-079 monotherapy and when combined with a backbone regimen of pomalidomide and dexamethasone (PomDex) in Phase 1, and to provide a preliminary evaluation of the clinical activity of TAK-079 monotherapy in Phase 2a in participants with r/r MM.

Conditions

Relapsed/Refractory; Multiple Myeloma

Keywords

Drug therapy, TAK-079, pomalidomide and dexamethasone, CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (7)

• Phase 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  TEAEs were any untoward medical occurrence (called an adverse event \[AE\]) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.

  From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)

• Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

  DLTs were defined as any of the following events: Grade 4 laboratory abnormalities, except those events that were clearly due to extraneous causes; nonhematologic TEAEs of grade greater than or equal to (\>=3) except grade 3 nausea/vomiting, fatigue lasting less than 72 hours, elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that resolves to grade less than or equal to (\<=)1 or baseline within 7 days, injection reaction (IR) that responds to symptomatic treatment; Hematologic TEAEs of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade \>=4, except grade \>=3 hemolysis, grade 3 low platelet or higher count with clinically meaningful bleeding; and an incomplete recovery from treatment-related toxicity causing a greater than (\>) 2-week delay in the next scheduled injection before the initiation of Cycle 2 will be considered a DLT.

  Cycle 1 (cycle length=28 days)

• Phase 1: Number of Participants With Grade 3 or Higher TEAEs

  AE Grades were evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE.

  From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)

• Phase 1: Number of Participants With Serious TEAEs

  TEAEs were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.

  From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)

• Phase 1: Number of Participants With TEAEs Leading to Treatment Discontinuation

  TEAEs leading to discontinuation were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug leading to discontinuation of any of the study treatment when given in combination.

  From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)

• Phase 1: Number of Participants With TEAEs Leading to Dose Modifications

  TEAEs were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Dose modification includes dose delayed, reduced, and drug discontinued permanently. Dose reduced includes scenarios where the dose was skipped, held, or missed. Dose modifications also refer to a modification of any drug in the study treatment when given in combination.

  From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)

• Phase 2a: Overall Response Rate (ORR)

  ORR is defined as the percentage of participants who achieved a partial response (PR) better during the study. PR is defined as \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 milligram per (mg/) 24 hours. If serum and urine M protein are not measurable, \>= 50% decrease in difference between involved and uninvolved free light chain (FLC) levels is required in place of M protein criteria.

  Up to approximately 3.7 years

Secondary Outcomes (15)

• Cmax: Maximum Observed Serum Concentration for TAK-079

  Cycles 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=28 days)

• Tmax: Time to Reach the Maximum Observed Serum Concentration (Cmax) for TAK-079

  Cycles 1 and 2: Day 1 pre-dose and at multiple time points (up to 190.95 hours) post-dose (cycle length=28 days)

• AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079

  Cycle 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=28 days)

• Phase 1: Overall Response Rate (ORR)

  Up to approximately 3.7 years

• Percentage of Participants With Minimal Response (MR)

  Up to approximately 3.7 years

Study Arms (7)

Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg

EXPERIMENTAL

Mezagitamab 45 mg, subcutaneously (SC), once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until progressive disease (PD), unacceptable toxicities or withdrawal due to other reasons.

Drug: Mezagitamab

Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg

EXPERIMENTAL

Mezagitamab 135 mg, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons.

Drug: Mezagitamab

Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg

EXPERIMENTAL

Mezagitamab 300 mg, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons.

Drug: Mezagitamab

Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg

EXPERIMENTAL

Mezagitamab 600 mg, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons.

Drug: Mezagitamab

Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg

EXPERIMENTAL

Mezagitamab 1200 mg, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons.

Drug: Mezagitamab

Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex

EXPERIMENTAL

Mezagitamab 300 mg, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter along with pomalidomide, at product-labelled dose, orally, once daily on Days 1 to 21 and dexamethasone, at product-labelled dose, orally, once on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD.

Drug: Mezagitamab; Drug: Pomalidomide; Drug: Dexamethasone

Phase 2a: Mezagitamab

EXPERIMENTAL

Mezagitamab, SC, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons. TAK-079 dose for this phase was to be determined based on review of the available safety, efficacy, pharmacokinetic, and pharmacodynamic data obtained from the Phase 1 portion of the study. However, Phase 2a of the study was not opened for enrollment due to changes in the Sponsor's overall clinical development plan.

Drug: Mezagitamab

Interventions

Mezagitamab DRUG

Mezagitamab subcutaneously.

Also known as: TAK-079

Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex; Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg; Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg; Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg; Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg; Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg; Phase 2a: Mezagitamab

Pomalidomide DRUG

Pomalidomide orally.

Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex

Dexamethasone DRUG

Dexamethasone orally.

Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of \<=2.
• Has received previous myeloma-specific therapy.
• In the Combination Cohort (TAK-079-PomDex) only must be able to take concurrent prophylactic anticoagulation per standard clinical practice as directed by the investigator and the Pomalyst product information.
• Documentation of RRMM as defined by the International Myeloma Working Group (IMWG) criteria.
• For Participants with MM, measurable disease defined as one of the following:
• Serum M-protein \>=0.5 g/dL (\>=5 gram per liter \[g/L\]).
• Urine M-protein \>=200 mg/24 hours.
• In participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum FLC assay result with involved FLC level \>=10 mg/dL (\>=100 milligram per liter \[mg/L\]), provided serum FLC ratio is abnormal.
• Prior therapy should meet all the following criteria:
• Participants in the dose Escalation Cohort (escalation phase) and participants in the dose Confirmation Cohort;
• Should be previously treated with at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and a steroid. Note: Participants who have had a previous autologous stem cell transplant will have additionally been exposed to an alkylating agent; however, participant who have not had a previous autologous stem cell transplant may not have been exposed to an alkylating agent per standard practice.
• Should be refractory or intolerant to at least 1 PI and at least 1 IMiD.
• Should either have received \>= 3 prior lines of therapy or should have received at least 2 prior lines of therapy if one of those lines included a combination of PI and IMiD.
• In phase 1, previous exposure to an anti-CD38 agent, as a single agent or in combination, is allowed but is not required. (Participants in the dose Escalation Cohort).
• In phase 1 dose Confirmation Cohort, cohorts of participants that are refractory at any time to at least 1 anti-CD38 agent or who are anti-CD38 naïve will be enrolled.

You may not qualify if:

• Sensory or motor neuropathy of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade \>=3.
• Have received allogeneic stem cell transplant.
• Have received anti-CD38 antibody therapy and do not fulfill a 180-day washout period before receiving TAK-079.
• Not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade \<=1 or baseline, excluding alopecia.
• Clinical signs of central nervous system (CNS) involvement of MM.
• Active chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active HIV, or cytomegalovirus (CMV) infection.
• POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or IgM myeloma.
• Positive Coombs tests at screening.
• For participants in the Combination Cohort (TAK-079-PomDex) only: participant has previously received pomalidomide or has hypersensitivity to thalidomide or lenalidomide.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

City of Hope - Duarte

Duarte, California, 91010, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Hospital-The Donald H. Ruttenberg Cancer Treatment Center

New York, New York, 10011, United States

Location

Weill Cornell Medical Center, Div. of Hematology Medical Oncology

New York, New York, 10065, United States

Location

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Krishnan AY, Patel KK, Mohan M, Jagannath S, Niesvizky R, Silbermann RW, Yu Z, Long T, McDonnell SRP, Berg D, Stockerl-Goldstein KE. Phase 1b study of the anti-CD38 antibody mezagitamab in patients with relapsed/refractory multiple myeloma. Blood Neoplasia. 2024 Sep 18;1(4):100043. doi: 10.1016/j.bneo.2024.100043. eCollection 2024 Dec.

  PMID: 40552138 DERIVED

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 20, 2018
• Study Start: April 20, 2018
• Primary Completion: January 28, 2022
• Study Completion: January 28, 2022
• Last Updated: February 24, 2023
• Results First Posted: February 24, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (7)