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A Study Of TAK-981 Given With Monoclonal Antibodies (mAbs) In Adults With Relapsed or Refractory Multiple Myeloma (RRMM)

Primary Purpose

Relapsed and/or Refractory Multiple Myeloma (RRMM)

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TAK-981
Mezagitamab
Daratumumab and Hyaluronidase-fihj
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed and/or Refractory Multiple Myeloma (RRMM) focused on measuring Drug Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participants must have RRMM with measurable disease:

    a) Has measurable disease defined as one of the following:

    • Serum M-protein ≥0.5 g/dL (≥5 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 free light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100 mg/L), provided serum FLC ratio is abnormal.
  2. Has undergone stem cell transplant or is considered transplant ineligible.
  3. Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory, or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 proteasome inhibitor (ie, bortezomib, ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have demonstrated disease progression with the last therapy.

5.Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

6.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.

Exclusion Criteria:

  1. Received treatment with systemic anticancer treatments within 14 days before the first dose of study drug.
  2. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of the first dose of TAK-981 and throughout the duration of this trial.
  3. Prior radiation therapy within 14 days of the first dose of TAK-981.
  4. Major surgery within 4 weeks before C1D1. participants should be fully recovered from any surgically related complications.
  5. Plasmapheresis within 28 days of randomization.
  6. Diagnosis of primary amyloidosis, Waldenström's disease, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), myelodysplastic syndrome, or myeloproliferative syndrome.
  7. With disease where the only measurable parameter is plasmacytoma.
  8. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
  9. Prior treatment with more than 1 anti-CD38 antibody.
  10. Requires the use of drugs known to prolong the corrected QT interval (QTc) (during Phase 1b only).
  11. History of QT interval with Fridericia's correction (QTcF) >480 ms.
  12. History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C infection.
  13. Systemic infection requiring systemic antibiotic therapy.
  14. Active or history pneumonitis.
  15. Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study drug.
  16. Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers.
  17. History of unstable cardiac comorbidities in the following 6 months.

Sites / Locations

  • Mayo Clinic Arizona - PPDS
  • Mayo Clinic Jacksonville - PPDS
  • Winship Cancer Institute, Emory University
  • Indiana University
  • American Oncology Partners of Maryland, PA
  • Mayo Clinic - Cancer Center - Rochester - PPDS
  • Oncology Hematology West (Omaha) - USOR
  • Weill Cornell Medical Center
  • TriHealth Cancer Institute
  • Baylor Sammons Cancer Center
  • Northeast Texas Cancer and Research Institute
  • Medical College of Wisconsin Cancer Center
  • Hopital Maisonneuve-Rosemont

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab

Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab

Phase 1b, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihj

Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab

Arm Description

Mezagitamab: A fixed dose of 600 mg subcutaneous (SC) injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks in Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 BIW intravenous (IV) infusion on Days 1, 4, 8, 11 and 15 in Cycle 1 and 2 (each Cycle is of 28 days) followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Mezagitamab: A fixed dose of 600 mg SC injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks from Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 QW IV infusion on Days 1, 8, 15, and 22 in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks. up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Daratumumab and hyaluronidase-fihj: 1800 mg SC injection QW once weekly in Cycles 1 and 2 , (each cycle is of 28 days) followed by every 2 weeks in Cycle 3 through 6 , followed by every 4 weeks up to Cycle 24 until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: As per dose and schedule of TAK-981 defined in Phase 1b Part 1.

TAK-981 at RP2D as determined in Phase 1b. Mezagitamab at a fixed dose of 600 mg SC injection or Daratumumab and Hyaluronidase-fihj at a fixed dose of 1800 mg weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycle 3 through 6, followed by every 4 weeks up to Cycle 24 or until disease progression unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Outcomes

Primary Outcome Measures

Phase 1b: Number of Participants with Treatment Emergent Adverse Events (TEAEs), By Severity at Each Dose Level
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death.
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT will be defined by NCI CTCAE, 5.0, Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade ≥3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 anemia or thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities leading to dose reduction/discontinuation. Delay in Cycle 2 by >14 days or missed >1 planned doses of TAK-981/mAb in Cycle 1 due to TEAEs.
Phase 2: Overall Response Rate (ORR) (Response of Atleast Partial Response [PR]) as Assessed by the Investigator's Based on International Myeloma Working Group (IMWG) Criteria
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) or better during the study as assessed by International Myeloma Working Group (IMWG) criteria.

Secondary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for TAK-981
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981
AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
t1/2z: Terminal Disposition Phase Half-life for TAK-981
CL: Total Clearance After Intravenous Administration for TAK-981
Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
Number of Participants with Anti-mezagitamab or anti-daratumumab antibody (ADA)
Serum Sparse Concentration of Mezagitamab or Daratumumab
Serum concentrations of mezagitumab and daratumumab will be evaluated during the study.
Phase 1b: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation
TAK-981-SUMO adduct formation in blood will be evaluated.
Phase 2: Number of Participants with TEAEs by Severity
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death.
Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator's Based on IMWG Criteria
ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) or better (determined by the investigator) during the study as assessed by IMWG criteria.
Phases 1b and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator's Based on IMWG Criteria
CBR is defined as percentage of participants who achieve at least a stable disease for a least 3 months or better.
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator's Based on IMWG Criteria
DOR is defined as a time from the time of first documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study as assessed by the investigator.
Phases 1b and 2: Time to Progression (TTP) as Assessed by the Investigator's Based on IMWG Criteria
TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression as assessed by the investigator.
Phases 1b and 2: Time to Next Treatment (TTNT) as Assessed by the Investigator's Based on IMWG Criteria
TTNT is defined as the time from the date of first dose of study drug to the date of the first dose of initiation of the next line of antineoplastic therapy, for any reason as assessed by the investigator.
Phases 1b and 2: Progression-free Survival (PFS) as Assessed by the Investigator's Based on IMWG Criteria
PFS is defined as time from the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study as assessed by the investigator.
Phases 1b and 2: Overall Survival (OS) as Assessed by the Investigator Based on IMWG Criteria
OS is defined as the time from the date of enrollment to the date of death as assessed by the investigator.
Phase 2: Percentage of Participants with MRD Negative Rate
MRD negativity is defined as the absence of MRD. MRD negativity rate is defined as percentage of participants who have achieved MRD negative status at 1 year.
Phase 2: Percentage of Participants with Minimal Residual Disease (MRD) Negative Status As Determined By Next-Generation Sequencing (NGS)
MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between as determined by NGS.
Phase 2: Number of Participants with Durable MRD Negative Rate
Durable MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between.

Full Information

First Posted
February 25, 2021
Last Updated
October 12, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT04776018
Brief Title
A Study Of TAK-981 Given With Monoclonal Antibodies (mAbs) In Adults With Relapsed or Refractory Multiple Myeloma (RRMM)
Official Title
A Phase 1b/2 Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-981 in Combination With Monoclonal Antibodies in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 20, 2021 (Actual)
Primary Completion Date
August 15, 2023 (Actual)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies (mAbs) to treat participants who have relapsed or refractory multiple myeloma (RRMM). The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination with anti-CD38 (mAbs) and to determine the recommended Phase 2 dose (RP2D). Participants will be on this combination treatment for 28-day cycles. They will continue with this treatment until disease progression or unacceptable toxicity.
Detailed Description
The drug being tested in this study is called TAK-981. TAK-981 in combination with an anti-CD38 monoclonal antibody (mAbs) is being tested to treat people who have RRMM. The study will include a dose escalation phase and a dose expansion phase. The study will enroll approximately 81 participants; approximately 30 participants in the dose escalation phase (Part 1) approximately 15 participants in (Part 2) and up to 36 participants in dose expansion phase (Part 2). Participants will receive escalating doses of TAK-981 in combination with fixed doses as follows: Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab Phase 1b, Part 2 - Dose Escalation: TAK-981 + Daratumumab and Hyaluronidase-fihj Once RP2D is determined in Phase 1, participants with RRMM will be enrolled in Phase 2. • Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab This multi-center trial will be conducted in North America. The overall time to participate in this study is 2 years. Participants will make multiple visits to the clinic, and progression-free survival follow-up for maximum up to 12 months after last dose of study drug.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed and/or Refractory Multiple Myeloma (RRMM)
Keywords
Drug Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab
Arm Type
Experimental
Arm Description
Mezagitamab: A fixed dose of 600 mg subcutaneous (SC) injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks in Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 BIW intravenous (IV) infusion on Days 1, 4, 8, 11 and 15 in Cycle 1 and 2 (each Cycle is of 28 days) followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
Arm Title
Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab
Arm Type
Experimental
Arm Description
Mezagitamab: A fixed dose of 600 mg SC injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks from Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 QW IV infusion on Days 1, 8, 15, and 22 in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks. up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
Arm Title
Phase 1b, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihj
Arm Type
Experimental
Arm Description
Daratumumab and hyaluronidase-fihj: 1800 mg SC injection QW once weekly in Cycles 1 and 2 , (each cycle is of 28 days) followed by every 2 weeks in Cycle 3 through 6 , followed by every 4 weeks up to Cycle 24 until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: As per dose and schedule of TAK-981 defined in Phase 1b Part 1.
Arm Title
Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab
Arm Type
Experimental
Arm Description
TAK-981 at RP2D as determined in Phase 1b. Mezagitamab at a fixed dose of 600 mg SC injection or Daratumumab and Hyaluronidase-fihj at a fixed dose of 1800 mg weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycle 3 through 6, followed by every 4 weeks up to Cycle 24 or until disease progression unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
TAK-981
Intervention Description
TAK-981 IV infusion.
Intervention Type
Drug
Intervention Name(s)
Mezagitamab
Intervention Description
Mezagitamab SC injection.
Intervention Type
Drug
Intervention Name(s)
Daratumumab and Hyaluronidase-fihj
Intervention Description
Daratumumab and Hyaluronidase-fihj SC injection.
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants with Treatment Emergent Adverse Events (TEAEs), By Severity at Each Dose Level
Description
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death.
Time Frame
Up to 24 months
Title
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLT will be defined by NCI CTCAE, 5.0, Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade ≥3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 anemia or thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities leading to dose reduction/discontinuation. Delay in Cycle 2 by >14 days or missed >1 planned doses of TAK-981/mAb in Cycle 1 due to TEAEs.
Time Frame
Through Cycle 1 (Each cycle is of 28 days)
Title
Phase 2: Overall Response Rate (ORR) (Response of Atleast Partial Response [PR]) as Assessed by the Investigator's Based on International Myeloma Working Group (IMWG) Criteria
Description
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) or better during the study as assessed by International Myeloma Working Group (IMWG) criteria.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
t1/2z: Terminal Disposition Phase Half-life for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
CL: Total Clearance After Intravenous Administration for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
Number of Participants with Anti-mezagitamab or anti-daratumumab antibody (ADA)
Time Frame
Up to 24 months
Title
Serum Sparse Concentration of Mezagitamab or Daratumumab
Description
Serum concentrations of mezagitumab and daratumumab will be evaluated during the study.
Time Frame
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose
Title
Phase 1b: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation
Description
TAK-981-SUMO adduct formation in blood will be evaluated.
Time Frame
Up to 24 months
Title
Phase 2: Number of Participants with TEAEs by Severity
Description
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death.
Time Frame
Up to 24 months
Title
Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator's Based on IMWG Criteria
Description
ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) or better (determined by the investigator) during the study as assessed by IMWG criteria.
Time Frame
Up to 24 months
Title
Phases 1b and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator's Based on IMWG Criteria
Description
CBR is defined as percentage of participants who achieve at least a stable disease for a least 3 months or better.
Time Frame
Up to 24 months
Title
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator's Based on IMWG Criteria
Description
DOR is defined as a time from the time of first documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study as assessed by the investigator.
Time Frame
Up to 24 months
Title
Phases 1b and 2: Time to Progression (TTP) as Assessed by the Investigator's Based on IMWG Criteria
Description
TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression as assessed by the investigator.
Time Frame
Up to 24 months
Title
Phases 1b and 2: Time to Next Treatment (TTNT) as Assessed by the Investigator's Based on IMWG Criteria
Description
TTNT is defined as the time from the date of first dose of study drug to the date of the first dose of initiation of the next line of antineoplastic therapy, for any reason as assessed by the investigator.
Time Frame
Up to 24 months
Title
Phases 1b and 2: Progression-free Survival (PFS) as Assessed by the Investigator's Based on IMWG Criteria
Description
PFS is defined as time from the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study as assessed by the investigator.
Time Frame
Up to 24 months
Title
Phases 1b and 2: Overall Survival (OS) as Assessed by the Investigator Based on IMWG Criteria
Description
OS is defined as the time from the date of enrollment to the date of death as assessed by the investigator.
Time Frame
Up to 24 months
Title
Phase 2: Percentage of Participants with MRD Negative Rate
Description
MRD negativity is defined as the absence of MRD. MRD negativity rate is defined as percentage of participants who have achieved MRD negative status at 1 year.
Time Frame
Up to 1 year
Title
Phase 2: Percentage of Participants with Minimal Residual Disease (MRD) Negative Status As Determined By Next-Generation Sequencing (NGS)
Description
MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between as determined by NGS.
Time Frame
Up to 24 months
Title
Phase 2: Number of Participants with Durable MRD Negative Rate
Description
Durable MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have RRMM with measurable disease: a) Has measurable disease defined as one of the following: Serum M-protein ≥0.5 g/dL (≥5 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 free light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100 mg/L), provided serum FLC ratio is abnormal. Has undergone stem cell transplant or is considered transplant ineligible. Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory, or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 proteasome inhibitor (ie, bortezomib, ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have demonstrated disease progression with the last therapy. 5.Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 6.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela. Exclusion Criteria: Received treatment with systemic anticancer treatments within 14 days before the first dose of study drug. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of the first dose of TAK-981 and throughout the duration of this trial. Prior radiation therapy within 14 days of the first dose of TAK-981. Major surgery within 4 weeks before C1D1. participants should be fully recovered from any surgically related complications. Plasmapheresis within 28 days of randomization. Diagnosis of primary amyloidosis, Waldenström's disease, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), myelodysplastic syndrome, or myeloproliferative syndrome. With disease where the only measurable parameter is plasmacytoma. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy. Prior treatment with more than 1 anti-CD38 antibody. Requires the use of drugs known to prolong the corrected QT interval (QTc) (during Phase 1b only). History of QT interval with Fridericia's correction (QTcF) >480 ms. History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C infection. Systemic infection requiring systemic antibiotic therapy. Active or history pneumonitis. Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study drug. Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers. History of unstable cardiac comorbidities in the following 6 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Arizona - PPDS
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic Jacksonville - PPDS
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322-1013
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
American Oncology Partners of Maryland, PA
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Mayo Clinic - Cancer Center - Rochester - PPDS
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Oncology Hematology West (Omaha) - USOR
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
TriHealth Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Northeast Texas Cancer and Research Institute
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Medical College of Wisconsin Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
35226739
Citation
Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.
Results Reference
derived
Links:
URL
https://clinicaltrials.takeda.com/study-detail/60423834eb9d7e001f5bc61b
Description
Related Info

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A Study Of TAK-981 Given With Monoclonal Antibodies (mAbs) In Adults With Relapsed or Refractory Multiple Myeloma (RRMM)

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