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Relapsed and/or Refractory Multiple Myeloma (RRMM)Phase 1/2NCT04776018

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

A Phase 1/2 study testing TAK-981, Mezagitamab and Daratumumab and Hyaluronidase-fihj in people with Relapsed and/or Refractory Multiple Myeloma (RRMM), run by Takeda at 13 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TAK-981, Mezagitamab and Daratumumab and Hyaluronidase-fihj
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
13 sitesin 2 countries
Study dates
20 Apr 2021to 9 Nov 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have RRMM with measurable disease:
  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

United States12 sites

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322-1013

  • American Oncology Partners of Maryland, PA

    Bethesda, Maryland, 20817

  • TriHealth Cancer Institute

    Cincinnati, Ohio, 45220

  • Baylor Sammons Cancer Center

    Dallas, Texas, 75246

  • Indiana University

    Indianapolis, Indiana, 46202

  • Mayo Clinic Jacksonville - PPDS

    Jacksonville, Florida, 32224

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Weill Cornell Medical Center

    New York, New York, 10065

  • Oncology Hematology West (Omaha) - USOR

    Omaha, Nebraska, 68130

  • Mayo Clinic - Cancer Center - Rochester - PPDS

    Rochester, Minnesota, 55905

  • Mayo Clinic Arizona - PPDS

    Scottsdale, Arizona, 85259

  • Northeast Texas Cancer and Research Institute

    Tyler, Texas, 75702

Other trials in United States

Canada1 site

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
TAK-981, Mezagitamab, Daratumumab and Hyaluronidase-fihj
Keywords
Drug Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-981Drug

    TAK-981 IV infusion.

  • MezagitamabDrug

    Mezagitamab SC injection.

  • Daratumumab and Hyaluronidase-fihjDrug

    Daratumumab and Hyaluronidase-fihj SC injection.

Study groups in NCT04776018
Study groupRoleWhat they receive
Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + MezagitamabExperimentalMezagitamab: 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.
Receives: Drug: TAK-981; Drug: Mezagitamab
Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + MezagitamabExperimentalMezagitamab: 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.
Receives: Drug: TAK-981; Drug: Mezagitamab
Phase 1b, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihjExperimentalDaratumumab 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.
Receives: Drug: TAK-981; Drug: Daratumumab and Hyaluronidase-fihj
Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or MezagitamabExperimentalTAK-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.
Receives: Drug: TAK-981; Drug: Mezagitamab; Drug: Daratumumab and Hyaluronidase-fihj

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)

    TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months)

  2. Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs

    The severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months)

  3. Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0

    DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (>=) 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 greater than (>) 14 days or missed >1 planned doses of TAK-981/monoclonal antibody (mAb) in Cycle 1 due to TEAEs.

    Measured: Cycle 1 (Cycle length = 28 Days)

  4. Phase 2: Overall Response Rate (ORR)

    ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5 percent (%) plasma cells in bone marrow (BM). PR: >50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by >90% or to less than (<) 200 milligrams per 24 hour (mg/24 h); If serum and urine M-protein were unmeasurable, >50% decrease in difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was >30%. In addition to the above listed criteria, if present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required.

    Measured: From date of treatment start to until date of first PD or death (whichever occurred first), up to 24 months

Secondary outcomes (29)

  1. Phase 1b, Part 1: Observed Plasma Concentration of TAK-981

    Observed plasma concentration of TAK-981 was reported.

    Measured: Cycle 1 Day 1: Pre-dose, at end of infusion (EOI), 2, 4, 6, and 24 hours post-dose; Cycle 1 Days 8 and 15: Pre-dose and EOI; Cycle 2 Days 1 and 15: Pre-dose and EOI (Cycle length = 28 days)

  2. Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981

    Cmax for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  3. Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

    Tmax for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  4. Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981

    AUC0-t for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  5. Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981

    AUC0-inf for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  6. Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981

    t1/2z for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  7. Phase 1b, Part 1, CL: Total Clearance for TAK-981

    CL for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  8. Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981

    Vss for TAK-981 was reported.

    Measured: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  9. Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer

    ADA positive was defined as participants who had confirmed positive ADA status in at least 1 post-baseline assessments. >=5-fold in ADA titer was defined as increase in the ADA titer value post-baseline of at least 5-fold from the positive ADA titer value at baseline.

    Measured: Baseline up to 12 months

  10. Phase 1b, Part 1: Serum Concentration of Mezagitamab

    Observed serum concentrations of mezagitumab was reported.

    Measured: Cycles 1, 2, 3, 4, 6, 7 and 12: Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)

  11. Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria

    ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow (BM). PR: >50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by >90% or to less than (<) 200 milligrams per 24 hour (mg/24 h); If the serum and urine M-protein were unmeasurable, >50% decrease in the difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was >30%. In addition to the above listed criteria, if present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required.

    Measured: From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 12 months)

  12. Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria

    CBR: % of participants with response of at least stable disease (SD) for >=3 months or better (stringent CR [sCR], immunophenotypic CR [iCR], molecular CR [mCR], CR, very good partial response [VGPR], PR, minimal response [MR] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, <5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >90% reduction in serum M-protein+urine M-protein level <100mg/24h. PR: >50% reduction of serum M-protein and in 24h urinary M-protein by >90% or to <200mg/24h. MR: >=25% but <=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD.

    Measured: From first dose of study drug until PD or death, whichever occurred first (up to 12 months)

  13. Phase 1b, Part 1: Duration of Response (DOR) Based on IMWG Criteria

    DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM. PR: >50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to <200 mg/24 h; If the serum and urine M-protein were unmeasurable, a >50% decrease in the difference between involved and uninvolved FLC levels was required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was >30%. In addition to the above listed criteria, if present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required. DOR was calculated for those participants with a confirmed PR or CR.

    Measured: From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (up to 12 months)

  14. Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria

    TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of >25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be >0.5 grams per deciliter [g/dL]). b) Urine M-component and/or (the absolute increase must be >200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be >10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be >10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium >11.5 mg/dL or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: From first dose of study drug to the date of the first documentation of PD or death, whichever occurred first (up to 12 months)

  15. Phases 1b, Part 1: Time to Next Treatment (TTNT)

    TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.

    Measured: From the date of first dose of study drug to the date of the first dose initiation of the next line of antineoplastic therapy (up to 12 months)

  16. Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria

    PFS was 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. PD was defined as increase of >25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be >0.5 g/dL). b) Urine M-component and/or (the absolute increase must be >200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be >10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: From the first dose of study drug to date of PD or death, whichever occurred first (up to 12 months)

  17. Phases 1b, Part 1: Overall Survival (OS)

    OS was defined as the time from the date of first dose to the date of death. OS was analyzed using Kaplan-Meier (KM) method. Participants were followed for survival after the last dose of study drug.

    Measured: From date of first dose of study drug up to death from any cause (up to 27 months)

  18. Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes

    Blood samples were collected to assess TAK-981-SUMO adduct formation. TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981.

    Measured: Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days)

  19. Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes

    Blood samples were collected to assess SUMO inhibition. SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains.

    Measured: Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days)

  20. Phase 2: Number of Participants With TEAEs and TEAEs by Severity

    TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. The severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.

    Measured: Up to 24 months

  21. Phase 2: CBR Based on IMWG Criteria

    CBR: percentage of participants with response of at least (SD for >=3 months or better sCR, iCR, mCR, CR, very good partial response [VGPR], PR, minimal response [MR] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, <5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >90% reduction in serum M-protein+urine M-protein level <100mg/24h. PR: >50% reduction of serum M-protein and in 24h urinary M-protein by >90% or to <200mg/24h. MR:>=25% but <=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD.

    Measured: Up to 24 months

  22. Phase 2: DOR Based on IMWG Criteria

    DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM. PR: >50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to <200 mg/24 h; If the serum and urine M-protein were unmeasurable, a >50% decrease in the difference between involved and uninvolved FLC levels was required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was >30%. In addition to the above listed criteria, if present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required.

    Measured: Up to 24 months

  23. Phase 2: TTP Based on IMWG Criteria

    TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of >25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be >0.5 grams per deciliter [g/dL]). b) Urine M-component and/or (the absolute increase must be >200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be >10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be >10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: Up to 24 months

  24. Phase 2: Time to Next Treatment (TTNT)

    TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.

    Measured: Up to 24 months

  25. Phase 2: PFS Based on IMWG Criteria

    PFS was 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. PD was defined as increase of >25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be >0.5 g/dL). b) Urine M-component and/or (the absolute increase must be >200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be >10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: Up to 24 months

  26. Phase 2: Overall Survival (OS)

    OS was defined as the time from the date of first dose to the date of death.

    Measured: Up to 24 months

  27. Phase 2: Percentage of Participants With MRD Negative Status as Determined by Next-Generation Sequencing (NGS)

    Measured: Up to 24 months

  28. Phase 2: Minimal Residual Disease (MRD) Negative Rate

    Measured: Up to 12 months

  29. Phase 2: Durable MRD Negative Rate

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2021
  2. Study start20 Apr 2021
  3. Primary completion2 Aug 2023
  4. Study completion9 Nov 2023

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04776018
Sponsor's protocol ID
TAK-981-1503
Status last verified
Sep 2024
First submitted
25 Feb 2021
Last updated
2 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 35226739

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TAK-981, Mezagitamab and Daratumumab and Hyaluronidase-fihj in people with Relapsed and/or Refractory Multiple Myeloma (RRMM), run by Takeda at 13 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) (time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04776018, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024.

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