A Study to Evaluate the Safety, Tolerability and Efficacy of Intravenous TAK-573 as Part of Combination Therapy in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)

NCT04392648 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: TAK-573-1002U1111-1249-1537
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of TAK-573 when used with dexamethasone and in combination with bortezomib, pomalidomide, or cyclophosphamide, in participants with RRMM.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (3)

• Number of Participants who Experienced at Least one Treatment Emergent Adverse Event (TEAE)

  Dose Escalation Phase: up to Cycle 17 (Cycle length = 21 days in Arm 1 and is = 28 days in Arms 2 and 3); Dose Expansion Phase: Cycle 17 up to 3 years (Cycle length = 21 days in Arm 4 and is = 28 days in Arms 5 and 6)

• Number of Participants with Clinically Significant Vital Signs Values, Clinically Significant Change From Baseline in Clinical Laboratory Values and 12-lead Electrocardiograms (ECG), and who Received any Concomitant Medications

  Dose Escalation Phase: up to Cycle 17 (Cycle length = 21 days in Arm 1 and is = 28 days in Arms 2 and 3); Dose Expansion Phase: Cycle 17 up to 3 years (Cycle length = 21 days in Arm 4 and is = 28 days in Arms 5 and 6)

• Dose Expansion Phase: Overall Response Rate (ORR)

  ORR is defined as the percentage of participants who achieved confirmed partial response (PR) or better during the study as assessed with International Myeloma Working Group (IMWG) Uniform Response Criteria. PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M protein and \>=90% reduction in urine M-protein or less than (\<) 200 milligram per 24 hour (mg/24 hour), or \>=50% decrease in uninvolved free light chain (FLC). At baseline, a \>=50% decrease in size of soft tissue plasmacytomas is required.

  Cycle 17 up to 3 years (Cycle length is equal to [=] 21 days in Arm 4 and is = 28 days in Arms 5 and 6)

Secondary Outcomes (17)

• Dose Escalation Phase, Cmax: Maximum Observed Serum Concentration for TAK-573

  Cycles 1 and 2 Day 1: pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days in Dose Escalation Phase Arm 1 and is = 28 days in Dose Escalation Phase Arms 2 and 3)

• Dose Escalation Phase, Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAK-573

  Cycles 1 and 2 Day 1: pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days in Dose Escalation Phase Arm 1 and is = 28 days in Dose Escalation Phase Arms 2 and 3)

• Dose Escalation Phase, AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-573

  Cycles 1 and 2 Day 1: pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days in Dose Escalation Phase Arm 1 and is = 28 days in Dose Escalation Phase Arms 2 and 3)

• Dose Escalation Phase, AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-573

  Cycles 1 and 2 Day 1: pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days in Dose Escalation Phase Arm 1 and is = 28 days in Dose Escalation Phase Arms 2 and 3)

• Dose Escalation Phase, Lambda (λ) z: Apparent Serum Terminal Disposition Rate Constant for TAK-573

  Cycles 1 and 2 Day 1: pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days in Dose Escalation Phase Arm 1 and is = 28 days in Dose Escalation Phase Arms 2 and 3)

Study Arms (6)

Escalation:TAK-573 0.1-1.5mg/kg+Bortezomib+Dexamethasone

EXPERIMENTAL

TAK-573 0.1 to 1.5 milligram per kilogram (mg/kg), infusion, intravenously, once, every 3 weeks in a 21-days treatment cycle, along with bortezomib 1.3 milligram per square meter (mg/m\^2), injection, subcutaneously, once on Days 1, 4, 8, and 11 and dexamethasone 40 milligram (mg) (20 mg if aged more than 75 years), tablets, orally on Days 1, 8, and 15 in each 21-days treatment cycle from Cycle 1 through Cycle 8. For participants who continue beyond Cycle 8, TAK-573 will be given as an infusion, intravenously, once, every 3 weeks in a 21-days treatment cycle with dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally from Cycle 9 through Cycle 17.

Drug: TAK-573; Drug: Bortezomib; Drug: Dexamethasone

Escalation:TAK-573 0.05-0.75mg/kg+Pomalidomide+Dexamethasone

EXPERIMENTAL

TAK-573 0.05 to 0.75 mg/kg, infusion, intravenously, once, every 4 weeks in a 28-days treatment cycle, along with pomalidomide 4 mg, capsules, orally, once daily from Days 1 through 21 and dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally, once on Days 1, 8, 15, and 22 in each 28-days treatment cycle from Cycle 1 through Cycle 17.

Drug: TAK-573; Drug: Pomalidomide; Drug: Dexamethasone

Escalation:TAK-573 0.1-1.5mg/kg+Cyclophosphamide+Dexamethasone

EXPERIMENTAL

TAK-573 0.1 to 1.5 mg/kg, infusion, intravenously, once, every 4 weeks in a 28-days treatment cycle, along with cyclophosphamide 300 mg/m\^2, tablets, orally, once on Days 1, 8, and 15 and dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally, once on Days 1, 8, 15, and 22 in each 28-days treatment cycle from Cycle 1 through Cycle 17.

Drug: TAK-573; Drug: Cyclophosphamide; Drug: Dexamethasone

Expansion: TAK-573 + Bortezomib + Dexamethasone

EXPERIMENTAL

TAK-573, infusion, intravenously, once, every 3 weeks in a 21-days treatment cycle, along with bortezomib 1.3 mg/m\^2, injection, subcutaneously, once on Days 1, 4, 8, and 11 and dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally, once on Days 1, 8, and 15 in each 21-days treatment cycle until disease progression, intolerable toxicity, withdrawal from study, or death (up to 3 years). The dose of TAK-573 for Dose Expansion Phase will be the RP2D and recommended dose for expansion (RAD) determined in the previous Dose Escalation Phase.

Drug: TAK-573; Drug: Bortezomib; Drug: Dexamethasone

Expansion: TAK-573 + Pomalidomide + Dexamethasone

EXPERIMENTAL

TAK-573, infusion, intravenously, once, every 4 weeks in a 28-days treatment cycle, along with pomalidomide 4 mg, capsules, orally, once daily from Days 1 through 21 and dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally, once on Days 1, 8, 15, and 22 in each 28-days treatment cycle until disease progression, intolerable toxicity, withdrawal from study, or death (up to 3 years). The dose of TAK-573 for Dose Expansion Phase will be the RP2D and RAD determined in the previous Dose Escalation Phase.

Drug: TAK-573; Drug: Pomalidomide; Drug: Dexamethasone

Expansion: TAK-573 + Cyclophosphamide + Dexamethasone

EXPERIMENTAL

TAK-573, infusion, intravenously, once, every 4 weeks in a 28-days treatment cycle, along with cyclophosphamide 300 mg/m\^2, tablets, orally, once on Days 1, 8, and 15 and dexamethasone 40 mg (20 mg if aged more than 75 years), tablets, orally, once on Days 1, 8, 15, and 22 in each 28-days treatment cycle until disease progression, intolerable toxicity, withdrawal from study, or death (up to 3 years). The dose of TAK-573 for Dose Expansion Phase will be the RP2D and RAD determined in the previous Dose Escalation Phase.

Drug: TAK-573; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

TAK-573 DRUG

TAK-573 intravenous infusion.

Escalation:TAK-573 0.05-0.75mg/kg+Pomalidomide+Dexamethasone; Escalation:TAK-573 0.1-1.5mg/kg+Bortezomib+Dexamethasone; Escalation:TAK-573 0.1-1.5mg/kg+Cyclophosphamide+Dexamethasone; Expansion: TAK-573 + Bortezomib + Dexamethasone; Expansion: TAK-573 + Cyclophosphamide + Dexamethasone; Expansion: TAK-573 + Pomalidomide + Dexamethasone

Pomalidomide DRUG

Pomalidomide capsules orally.

Escalation:TAK-573 0.05-0.75mg/kg+Pomalidomide+Dexamethasone; Expansion: TAK-573 + Pomalidomide + Dexamethasone

Bortezomib DRUG

Bortezomib injection subcutaneously.

Escalation:TAK-573 0.1-1.5mg/kg+Bortezomib+Dexamethasone; Expansion: TAK-573 + Bortezomib + Dexamethasone

Cyclophosphamide DRUG

Cyclophosphamide tablets orally.

Escalation:TAK-573 0.1-1.5mg/kg+Cyclophosphamide+Dexamethasone; Expansion: TAK-573 + Cyclophosphamide + Dexamethasone

Dexamethasone DRUG

Dexamethasone tablets orally.

Escalation:TAK-573 0.05-0.75mg/kg+Pomalidomide+Dexamethasone; Escalation:TAK-573 0.1-1.5mg/kg+Bortezomib+Dexamethasone; Escalation:TAK-573 0.1-1.5mg/kg+Cyclophosphamide+Dexamethasone; Expansion: TAK-573 + Bortezomib + Dexamethasone; Expansion: TAK-573 + Cyclophosphamide + Dexamethasone; Expansion: TAK-573 + Pomalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Received \>=2 prior lines of therapy, including treatment with lenalidomide and a proteasome inhibitor.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• With measurable disease, defined as at least 1 of the following:
• Serum M protein \>=500 mg/dL (\>=5 gram per liter \[g/L\]) on serum protein electrophoresis (SPEP).
• Urine M protein \>=200 mg/24 hours on urine protein electrophoresis (UPEP).
• Serum FLC assay result with an involved FLC level \>=10 mg/dL (\>=100 milligram per liter \[mg/L\]), provided the serum FLC ratio is abnormal.
• Has adequate organ function as determined by the following laboratory values:
• Absolute neutrophil count (ANC) \>=1000 per cubic millimeter (/mm\^3) (\>=1.0\*10\^9 \[per liter\]/L)
• Platelets \>=75,000/mm\^3 (\>=75\*10\^9/L)
• Hemoglobin \>=80 g/L
• Creatinine clearance \>=30 milliliter per minute (mL/min)
• Total serum bilirubin \<=1.5\*upper limit normal (ULN), \>=2.0\*ULN for participants with Gilbert's syndrome
• Liver transaminases (alanine aminotransferase \[ALT\]/ aspartate aminotransferase \[AST\]) Serum ALT or AST \<=3.0\*ULN (\<5\*ULN if enzyme elevations are due to MM-related diffuse hepatic infiltrations).
• Has received the final dose of any of the following treatments/procedures within the specified minimum intervals before first dose of TAK-573:
• Chemotherapy, including proteasome inhibitors and immunomodulatory imide drug.(IMiDs) 14 days

You may not qualify if:

• Has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia or IgM myeloma, lymphoplasmacytic lymphoma, or plasma cell leukemia.
• Previous intolerance to combination agent.
• For the pomalidomide expansion group only: no prior treatment with pomalidomide.
• Inability to take prophylaxis needed for combination agent (deep vein thrombosis prophylaxis for pomalidomide, antiviral prophylaxis for proteasome inhibitor).
• Who have received autologous stem cell transplant (SCT) within 60 days before first infusion of TAK-573 or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
• Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade \<=1 or baseline, except for sensory or motor neuropathy which should have recovered to Grade \<=2 or baseline, Grade \<2 for participants receiving bortezomib.
• Has a chronic condition requiring the use of systemic corticosteroids \>10 milligram per day (mg/day) of prednisone or equivalent.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D LLC: lead

MeSH Terms

Interventions

pomalidomide; Bortezomib; Cyclophosphamide; Dexamethasone

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

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

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 19, 2020
• Study Start: June 24, 2020
• Primary Completion: November 10, 2023
• Study Completion: November 10, 2023
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share