Clinical Trials /

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

NCT04776018

Description:

TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies to treat participants who have relapsed or refractory multiple myeloma. The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination with anti-CD38 monoclonal antibodies. Participants will be on this combination treatment for 28-day cycles. They will continue with this treatment until disease progression or unacceptable toxicity.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Of TAK-981 Given With Monoclonal Antibodies In Adults With Relapsed or Refractory Multiple Myeloma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TAK-981-1503
  • NCT ID: NCT04776018

Conditions

  • Relapsed and/or Refractory Multiple Myeloma (RRMM)

Interventions

DrugSynonymsArms
TAK-981Phase 1, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab
MezagitamabPhase 1, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab
Daratumumab and Hyaluronidase-fihjPhase 1, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihj

Purpose

TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies to treat participants who have relapsed or refractory multiple myeloma. The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination with anti-CD38 monoclonal antibodies. 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 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 patients, 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 of fixed doses as follows:

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

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

        -  Phase 1, 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 48 months. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + MezagitamabExperimentalMezagitamab: A fixed dose of 600 mg subcutaneous (SC) injection once weekly x 8 doses, then once every 2 weeks for 8 doses, then monthly 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 for 8 doses, then monthly up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
  • TAK-981
  • Mezagitamab
Phase 1, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + MezagitamabExperimentalMezagitamab: A fixed dose of 600 mg SC injection once weekly x 8 doses, then once every 2 weeks for 8 doses, then monthly 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 once weekly x 8 doses, then once every 2 weeks x 8 doses, then monthly up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
  • TAK-981
  • Mezagitamab
Phase 1, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihjExperimentalDaratumumab and hyaluronidase-fihj: 1800 mg SC injection QW once weekly x 8 doses, then every 2 weeks x 8 doses, then monthly 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
  • 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 x 8 doses, then every 2 weeks x 8 doses, then monthly up to Cycle 24 or until disease progression unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.
  • TAK-981
  • Mezagitamab
  • Daratumumab and Hyaluronidase-fihj

Eligibility Criteria

        Inclusion Criteria:

          1. Participants must have RRMM with measurable disease:

               1. 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 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.

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

          3. 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 1 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 within 4 weeks of initiation of study drug.

         16. Receiving strong or moderate Cytochrome P450 (CYP3A4/5) inhibitors or inducers.

         17. History of unstable cardiac comorbidities in the following 6 months.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Number of Participants with Treatment Emergent Adverse Events (TEAEs), By Severity at Each Dose Level
Time Frame:Up to 24 months
Safety Issue:
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. The severity of TEAEs will be based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Blood
Time Frame:Up to 24 months
Safety Issue:
Description:TAK-981-SUMO adduct formation and pathway inhibition in blood will be evaluated.
Measure:Phase 2: Number of Participants with TEAEs by Severity
Time Frame:Up to 24 months
Safety Issue:
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. The severity of TEAEs will be based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (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.
Measure:Phase 1: Overall Response Rate (ORR) as Assessed by the Investigator's Based on IMWG Criteria
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phases 1 and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:CBR is defined as percentage of participants who achieve at least a stable disease for a least 3 months or better.
Measure:Phase 1: Duration of Response (DOR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phases 1 and 2: Time to Progression (TTP) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phases 1 and 2: Time to Next Treatment (TTNT) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phases 1 and 2: Progression-free Survival (PFS) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phases 1 and 2: Overall Survival (OS) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:OS is defined as the time from the date of enrollment to the date of death as assessed by the investigator.
Measure:Phase 2: Percentage of Participants with Minimal Residual Disease (MRD) Negative Status As Determined By Next-Generation Sequencing (NGS)
Time Frame:Up to 24 months
Safety Issue:
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.
Measure:Phase 2: Percentage of Participants with MRD Negative Rate
Time Frame:Up to 1 year
Safety Issue:
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.
Measure:Phase 2: Number of Participants with Durable MRD Negative Rate
Time Frame:Up to 24 months
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Takeda

Trial Keywords

  • Drug Therapy

Last Updated

June 9, 2021