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

Browse trials for

• Recurrence 3,523Registry's first term
• Multiple Myeloma 3,760Primary · reclassified

Keywords

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

Multiple Myeloma Reclassified

3,760 studies on the registry are indexed under Multiple Myeloma; 769 are open to participants now.

This study's enrollment of 50 is above the median of 41 across 3,005 interventional studies indexed under Multiple Myeloma.

Lead sponsor

Millennium Pharmaceuticals, Inc. is the lead sponsor of 178 studies on the registry; none are open to participants now.

Of its 74 completed or terminated interventional studies of FDA-regulated products, 73 (99%) have results posted.

First submitted after Millennium Pharmaceuticals, Inc. became part of Takeda.

Study arms

• Experimental
  Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg

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

  Drug: Mezagitamab

• Experimental
  Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg

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

  Drug: Mezagitamab

• Experimental
  Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg

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

  Drug: Mezagitamab

• Experimental
  Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg

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

  Drug: Mezagitamab

• Experimental
  Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg

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

  Drug: Mezagitamab

• Experimental
  Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex

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

  Drug: Mezagitamab · Drug: Pomalidomide · Drug: Dexamethasone

• Experimental
  Phase 2a: Mezagitamab

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

  Drug: Mezagitamab

Interventions

• DrugMezagitamab

  Mezagitamab subcutaneously.

  Also known as: TAK-079

• DrugPomalidomide

  Pomalidomide orally.

• DrugDexamethasone

  Dexamethasone orally.

Primary outcomes

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

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

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

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

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

   Time frame: Cycle 1 (cycle length=28 days)

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

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

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

4. Phase 1: Number of Participants With Serious TEAEs

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

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

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

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

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

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

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

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

7. Phase 2a: Overall Response Rate (ORR)

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

   Time frame: Up to approximately 3.7 years

Secondary outcomes

1. Cmax: Maximum Observed Serum Concentration for TAK-079

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

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

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

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

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

4. Phase 1: Overall Response Rate (ORR)

   ORR is defined as the percentage of participants who achieved a partial response (PR) or better during the study. PR is defined as \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 hours. If the serum and urine M-protein were not measurable, 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 were not measurable, and serum FLC was also not measurable, ≥50% reduction in bone marrow plasma cells was required in place of M-protein, provided the baseline percentage was ≥30%. In addition to the above criteria, if present at baseline, ≥50% reduction in the size of soft tissue plasmacytomas was also required. Two consecutive assessments were needed; no known evidence of progressive or new bone lesions if radiographic studies were performed. Percentages are rounded off to whole number at the nearest decimal.

   Time frame: Up to approximately 3.7 years

5. Percentage of Participants With Minimal Response (MR)

   MR is defined as \>=25% but \<=49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%. Percentages are rounded off to whole number at the nearest decimal.

   Time frame: Up to approximately 3.7 years

6. Percentage of Participants With Positive Anti-drug Antibodies (ADA)

   Percentages are rounded off to whole number at the nearest decimal.

   Time frame: Up to approximately 3.7 years

7. Phase 2a: Number of Participants With DLTs

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

8. Phase 2a: Number of Participants Reporting One or More TEAEs

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

9. Phase 2a: Number of Participants With TEAEs Leading to Dose Modifications

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

10. Phase 2a: Number of Participants With TEAEs Leading to Treatment Discontinuation

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

11. Phase 2a: Duration of Response (DOR)

    DOR is the time from date of first documentation of response to date of first documented PD. PD is increase of \>=25% from lowest response value in any of following:Serum M-protein(increase must be \>=0.5 gram per deciliter\[g/dL\];serum M component increases \>=1 g/dL are sufficient to define relapse if starting M component is \>=5 g/dL),and/or urine M-protein(increase must be \>=200 mg/24 hour), and/or only in participants without measurable serum and urine M-protein levels, difference between involved/uninvolved FLC levels (increase must be \>10 mg/dL), and only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell percentage (percentage must be \>=10%) or definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or soft tissue plasmacytomas, and development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.

    Time frame: Up to approximately 3.7 years

12. Phase 2a: Progression Free Survival (PFS)

    PFS is time from the date of the first dose until the earliest date of disease progression (PD). PD is increase of \>=25% from lowest response value in any of following: Serum M-protein (increase must be \>=0.5 g/dL; serum M component increases \>=1 g/dL are sufficient to define relapse if starting M component is \>=5 g/dL),and/or urine M-protein (increase must be \>=200 mg/24 hour), and/or only in participants without measurable serum and urine M-protein levels, difference between involved/uninvolved FLC levels (increase must be \>10 mg/dL), and only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell percentage (percentage must be \>=10%) or definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or soft tissue plasmacytomas, and development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.

    Time frame: Up to approximately 3.7 years

13. Phase 2a: Overall Survival (OS)

    OS is defined as the time from the date of first dose to the date of death due to any cause.

    Time frame: Up to approximately 3.7 years

14. Phase 2a: Time to Response (TTR)

    TTR is defined as the time from the date of the first dose to the date of the first documentation of response (PR \[partial response\] or better). PR is defined as \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 hours.

    Time frame: Up to approximately 3.7 years

15. Phase 1: RP2D of TAK-079

    RP2D was determined by dose escalating monotherapy groups.

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

Baseline characteristics

Study documents

• Study protocol ↗ · Apr 2, 2019
• Statistical analysis plan ↗ · Jan 11, 2021

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

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.

Data sharing details ↗ · vivli.org