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A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

Sponsor
Takeda (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03215030
Collaborator
(none)
336
Enrollment
105
Locations
7
Arms
90.6
Anticipated Duration (Months)
3.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main aims of this 3-part study are as follows:

Part 1: To determine any side effects from modakafusp alfa single treatment and how often they occur. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found.

Part 2: To assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. Dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants.

Part 3: To find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa.

Participants will receive modakafusp alfa at one of two doses which will be given through a vein.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

The drug being tested in this study, and which will be given through a vein, is called modakafusp alfa (TAK-573 ) as single agent or in combination with dexamethasone. The study will determine the safety, tolerability, and efficacy of modakafusp alfa as single agent and in combination with dexamethasone in participants with relapsed/refractory multiple myeloma (RRMM). The study consists of 3 Parts:

Part 1: Dose Escalation, Part 2: Dose Expansion, Part 3: Dose Extension

The study will enroll approximately 65 participants in Part 1, 35 in Part 2, and 236 in Part 3. Participants will be assigned to one of the following treatment groups in Parts 1 and 2 of the study. Participants will be randomly assigned in Part 3 of the study as given below:

  • Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg

  • Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD

  • Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD

  • Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD

  • Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg

  • Part 3 (Dose Extension): Modakafusp alfa 120 mg

  • Part 3 (Dose Extension): Modakafusp alfa 240 mg

The Part 1 (Dose Escalation) portion of the study will follow a 3+3 dose escalation design to evaluate once-weekly up to 4 different schedules of administration of modakafusp alfa starting at 0.001 mg/kg for dose limiting toxicity (DLT) evaluation and to determine the maximum tolerated dose (MTD) or an optimal biological dose (OBD) for assessments in Part 2.

The Part 2 (Dose Expansion) will further assess the safety profile of modakafusp alfa and its efficacy at MTD or OBD.

For Part 3 (Dose Extension) participants will be randomized 1:1 to receive single-agent modakafusp alfa 120 mg or 240 mg Q4W.

Parts 1 and 2 will be conducted at multiple centers in the United States. Part 3 will be conducted worldwide. The maximum treatment duration in this study is up to 12 months (Parts 1 and 2) or until disease progression (Part 3) and overall time to participate in the study is approximately up to 90 months. Participants with clinical benefit may continue treatment after sponsor approval.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
336 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Modakafusp Alfa (TAK-573) as a Single Agent in Patients With Relapsed Refractory Multiple Myeloma
Actual Study Start Date :
Oct 4, 2017
Anticipated Primary Completion Date :
May 25, 2023
Anticipated Study Completion Date :
Apr 23, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg

Modakafusp alfa 0.001 up to 14 milligram per kilogram (mg/kg), infusion, intravenously (IV), once every week (Q1W) on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Drug: Modakafusp alfa
Modakafusp alfa intravenous infusion.
Other Names:
  • TAK-573
  • TEV-48573

    		•
    Experimental: Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD

    Modakafusp alfa TBD, infusion, IV, once every 2 weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    		•
    Experimental: Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD

    Modakafusp alfa TBD, infusion, IV, once every 3 weeks (Q3W) on Day 1 of each 21-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    		•
    Experimental: Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD

    Modakafusp alfa TBD, infusion, IV, once every 4 weeks (Q4W) on Day 1 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    		•
    Experimental: Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg

    Dose(s) for Phase 2 will be based on safety and tolerability results from the preceding Phase 1 dose escalation cohorts. Participants in Phase 2 cohorts will receive modakafusp alfa TBD as a single agent. Participants in at least 1 cohort will receive modakafusp alfa TBD and modakafusp alfa TBD and dexamethasone 40 mg, orally, once weekly of each 28-day treatment cycle until treatment discontinuation.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    • Drug: Dexamethasone
    Dexamethasone.
    Experimental: Part 3 (Dose Extension): Modakafusp alfa 120 mg

    Participants will receive modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    		•
    Experimental: Part 3 (Dose Extension): Modakafusp alfa 240 mg

    Participants will receive modakafusp alfa 240 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

    Drug: Modakafusp alfa
    Modakafusp alfa intravenous infusion.
    Other Names:
  • TAK-573
  • TEV-48573

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) [Up to approximately 90 months]

      An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A TEAE is defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.

    2. Part 1: Percentage of Participants With Dose-limiting Toxicities (DLTs) [Up to Cycle 1 (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      DLTs will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. Nonhematologic TEAEs of NCI CTCAE Grade ≥3 clearly unrelated to the underlying disease and occurring during the first cycle will be considered DLTs.

    3. Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs [Up to approximately 90 months]

      TEAEs Grades will be evaluated as per NCI CTCAE, Version 5.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; 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.

    4. Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs) [Up to approximately 90 months]

      An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

    5. Part 1: Percentage of Participants Who Discontinue the Treatment Because of TEAE [Up to approximately 90 months]

      A TEAE is defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.

    6. Part 1: Percentage of Participants With Dose Modifications: Dose Delay [Up to approximately 90 months]

    7. Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions [Up to approximately 90 months]

    8. Part 1: Percentage of Participants With Dose Modifications: Dose Reductions [Up to approximately 90 months]

    9. Part 1: Percentage of Participants With Clinically Significant Laboratory Values [Up to approximately 90 months]

      Laboratory values will include hematology, chemistry, and urine analysis.

    10. Part 1: Percentage of Participants With Clinically Significant Vital Signs Measurements [Up to approximately 90 months]

      Vital signs will include temperature, pulse, respiratory rate, oxygen saturation, and blood pressure.

    11. Part 2: Overall Response Rate (ORR) [Up to approximately 90 months]

      ORR is defined as the percentage of participants who achieved a partial response rate (PR) or better during the study as defined by International Myeloma Working Group (IMWG) Uniform Response Criteria.

    12. Part 3: Overall Response Rate (ORR) Assessed by Independent Review Committee (IRC) [Up to approximately 90 months]

      ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria assessed by IRC.

    Secondary Outcome Measures

    1. Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events [Up to approximately 90 months]

      Percentage of participants with TEAEs meeting DLT definition that occur after phase (P) 1 Cycle (C) 1 will be reported. Toxicity will be evaluated as per the NCI CTCAE, Version 5.0. The hematologic TEAEs of Grade ≥3 clearly unrelated to the underlying disease and occur during the first cycle that is considered DLTs: Grade ≥3 hemolysis; Grade 4 neutropenia for >7 consecutive days; Grade 4 thrombocytopenia for >14 consecutive days; Grade 3 thrombocytopenia with clinically significant bleeding; Any other Grade ≥4 hematologic toxicity except for Grade 4 lymphopenia. An incomplete recovery from treatment-related toxicity causing >2-week delay in the next scheduled infusion before the initiation of C2 will be considered a DLT. Frequencies and other TEAEs occur over the course of extended treatment with study drug, including dose modification, treatment discontinuation, and clinically significant laboratory values and vital signs.

    2. Part 1: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    3. Part 1: Tmax: Time to Reach the Cmax for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    4. Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    5. Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa [A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    6. Part 1: λz: Terminal Disposition Rate Constant for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    7. Part 1: T1/2: Terminal Elimination Half-life for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    8. Part 1: CL: Clearance for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    9. Part 1: Vss: Volume of Distribution at Steady State for Modakafusp alfa [Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)]

      PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

    10. Parts 1, 2 and 3: Percentage of Participants with Positive Anti-drug Antibodies (ADA) [Up to approximately 90 months]

    11. Part 1: Objective Response Rate (ORR) [Up to approximately 90 months]

      ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria.

    12. Parts 1 and 2: Clinical Benefit Rate (CBR) [Up to approximately 90 months]

      CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.

    13. Parts 1 and 2: Disease Control Rate (DCR) [Up to approximately 90 months]

      DCR is defined as the percentage of participants who achieved a stable disease (SD) or better during the study as defined by IMWG Uniform Response Criteria.

    14. Parts 1, 2 and 3: Duration of Response (DOR) [Up to approximately 90 months]

      DOR is defined as the time from the date of first documentation of response PR or better to the time of disease progression or death, whichever occurs first.

    15. Parts 1 and 2: Time to Response [Up to approximately 90 months]

      Time to response is defined as the time from first dose to the date of first documentation of response (PR or better).

    16. Parts 1, 2 and 3: Progression Free Survival (PFS) [Up to approximately 90 months]

      PFS is defined as the time from the date of enrollment until the date of PD or death due to any cause, whichever occurs first as defined by IMWG Criteria.

    17. Parts 2 and 3: Overall Survival (OS) [Up to approximately 90 months]

    18. Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa [Up to approximately 90 months]

    19. Part 2: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa [Up to approximately 90 months]

    20. Part 2: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa [Up to approximately 90 months]

    21. Part 2: λz: Terminal Disposition Rate Constant for Modakafusp alfa [Up to approximately 90 months]

    22. Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa [Up to approximately 90 months]

    23. Part 2: CL: Clearance for Modakafusp alfa [Up to approximately 90 months]

    24. Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa [Up to approximately 90 months]

    25. Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa [Up to approximately 90 months]

    26. Part 3: Objective Response Rate (ORR) by Investigator Assessment [Up to approximately 90 months]

      ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria assessed by investigators.

    27. Part 3: Clinical Benefit Rate (CBR) by IRC and Investigator assessment [Up to approximately 90 months]

      CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.

    28. Part 3: Duration of Clinical Benefit [Up to approximately 90 months]

      Duration of clinical benefit is defined as the time from first documented evidence of confirmed MR or better until the earliest date of a confirmed PD per IMWG, or death among patients who achieve a confirmed MR or better.

    29. Part 3: Disease Control Rate (DCR) by IRC and Investigator Assessment [Up to approximately 90 months]

      DCR is defined as the percentage of participants who achieved a stable disease (SD) or better during the study as defined by IMWG Uniform Response Criteria.

    30. Part 3: Duration of Disease Control [Up to approximately 90 months]

      Duration of disease control is defined as the time from first documented evidence of SD or better until the earliest date of a confirmed PD per IMWG, or death among patients who achieve a SD or better.

    31. Part 3: Time to Progression (TTP) by IRC and Investigator Assessment [Up to approximately 90 months]

      TTP is defined as the time from the date of the first dose until the earliest date of confirmed PD per IMWG, or death due to PD.

    32. Part 3: Rate of Minimal Residual Disease (MRD) Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR [Up to approximately 90 months]

      MRD negativity at a sensitivity of 10^-5 is defined as patients who are MRD negative at a sensitivity of 10^-5 in patients achieving suspected complete response (CR). CR is defined as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required.

    33. Part 3:Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR [Up to approximately 90 months]

      Duration of MRD negativity (10^-5) is defined as the time from the first MRD negative status (10^-5) to the earliest date of the MRD positive status (10^-5), confirmed PD per IMWG or death.

    34. Part 3: Percentage of Participants With Adverse Events (AEs) [Up to approximately 90 months]

      An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.

    35. Part 3: Percentage of Participants With Serious Adverse Events (SAEs) [Up to approximately 90 months]

      An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

    36. Part 3: Percentage of Participants With Clinically Significant Laboratory Values [Up to approximately 90 months]

      Laboratory values will include hematology, chemistry, and urine analysis.

    37. Part 3: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Status [Up to approximately 90 months]

      ECOG is a grade, where grade 0: Normal activity. Grade 1: Symptoms but ambulatory. Grade 2: In bed <50% of the time. Grade 3: In bed >50% of the time. Grade 4: 100% bedridden. Grade 5: Dead.

    38. Part 3: Health Care Utilization: Length of Hospital Stays [Up to approximately 90 months]

    39. Part 3: Percentage of Participants With Neutralizing Antibodies (NAb) [Up to approximately 90 months]

    40. Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter [Up to approximately 90 months]

      Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits.

    41. Part 3: Patient-reported Outcome (PRO): Instrument European Organisation for Research and Treatment of Cancer QLQ Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20) [Up to approximately 90 months]

      The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image and future perspective), and 2 symptoms scales (disease symptoms and side effects of treatment). The QLQ-MY20 raw scores are converted into scale scores ranging from 0 to 100. For the symptom scales, lower scores represent better functioning. All items in this questionnaire have a recall period of 1 week.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    For Parts 1 and 2:
    1. Has MM defined by the IMWG criteria with evidence of disease progression and:

    • In need of additional myeloma therapy as determined by the investigator.

    • Has previously received at least 3 lines of myeloma therapy (for example, containing an Immunomodulatory imide drug [IMiD], a proteasome inhibitor [PI], an alkylating agent, and/or an anti-CD38 as single agents or in combination).

    • Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD.

    For Part 3:
    1. Has MM defined by the IMWG criteria with evidence of disease progression and:

    • In need of additional myeloma therapy as determined by the investigator.

    • Has previously received at least 3 lines of myeloma therapy.

    • Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. Participants who are primary refractory, meaning they never achieved at least a MR with any previous treatment line, are not eligible.

    1. For participants in Part 2 and 3 only: Measurable disease is defined as :

    2. Serum M-protein ≥500 mg/dL (≥5 g/L)

    3. Urine M-protein ≥200 mg/24 hours.

    4. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.

    5. During Part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter) detected by physical examination or imaging.

    6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

    Exclusion Criteria:
    For Parts 1 and 2:

    1. Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).

    2. Who have received autologous stem cell transplant (SCT) 60 days before first infusion of modakafusp alfa or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.

    3. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to (≤) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to ≤ Grade 2 or baseline.

    4. Has clinical signs of central nervous system involvement of MM.

    For Part 3:

    • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded.

    • In addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory MM, current central nervous system involvement of MM, myelodysplastic syndrome, myeloproliferative syndrome, or have had a 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Highlands Oncology Group Springdale Arkansas United States 72762
    2 Los Angeles Cancer Network - Glendale Adventist Medical Center Glendale California United States 91204
    3 University of California Irvine Orange California United States 92868
    4 Office of James R. Berenson MD West Hollywood California United States 90069
    5 Smilow Cancer Hospital at Yale New Haven New Haven Connecticut United States 06520
    6 Winship Cancer Institute of Emory University Atlanta Georgia United States 30322
    7 Northwestern Medicine - Northwestern Medical Group Chicago Illinois United States 60611
    8 Loyola University Medical Center Maywood Illinois United States 60153
    9 Johns Hopkins Hospital Baltimore Maryland United States 21287
    10 Boston Medical Center Boston Massachusetts United States 02118
    11 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    12 Univeristy of Nebraska Medical Center Omaha Nebraska United States 68198
    13 USOR - Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89119
    14 John Theurer Cancer Center Hackensack New Jersey United States 07601
    15 Montefiore Medical Center Bronx New York United States 10467
    16 Roswell Park Comprehensive Cancer Center Buffalo New York United States 14263
    17 University of Rochester Rochester New York United States 14627
    18 Levine Cancer Center Charlotte North Carolina United States 28402
    19 Levine Cancer Institute - Concord Concord North Carolina United States 28205
    20 Duke University Medical Center Durham North Carolina United States 27710
    21 Gabrail Cancer Center Canton Ohio United States 44718
    22 The Ohio State University Columbus Ohio United States 43210
    23 Oregon Health and Science University Portland Oregon United States 97239
    24 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    25 Lumi Research Houston Texas United States 77002
    26 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    27 University Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792
    28 British Columbia Cancer Agency Vancouver Centre Vancouver British Columbia Canada V5Z 4E6
    29 Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
    30 Victoria Hospital London Ontario Canada N6A 4G5
    31 Centre de Recherche du CHUM Montreal Quebec Canada H2X 0C1
    32 Sir Mortimer B. Davis Jewish General Hospital Montreal Quebec Canada H3T 1E2
    33 Beijing Chao-Yang Hospital Beijing Beijing China 100020
    34 Beijing Chao-Yang Hospital Beijing Beijing China 100040
    35 Peking University People's Hospital Beijing Beijing China 100044
    36 Peking University Third Hospital Beijing Beijing China 100089
    37 Sun Yat-Sen University Cancer Center Guangzhou Guangdong China 510060
    38 Henan Cancer Hospital Zhengzhou Henan China 450003
    39 Wuhan Union Hospital Wuhan Hubei China 430023
    40 Zhongnan Hospital of Wuhan University Wuhan Hubei China 430071
    41 Nanjing Drum Tower Hospital Nanjing Jiangsu China 210008
    42 The First Affiliated Hospital of Soochow University - Suzhou First People's Hospital Suzhou Jiangsu China 215006
    43 Tianjin Medical University Cancer Institute & Hospital Tianjin Tianjin China 300060
    44 The First Affiliated Hospital, Zhejiang University Hangzhou Zhejiang China 310003
    45 Fakultni Nemocnice Olomouc Olomouc Severomoravsky KRAJ Czechia 775 20
    46 Fakultni Nemocnice Brno Brno Czechia 625 00
    47 Univerzita Karlova - 1. Lekarska Fakulta Praha Czechia 128 08
    48 Institut de cancerologie Strasbourg Europe Strasbourg Alsace France 67200
    49 Centre Hospitalier Universitaire Henri Mondor Creteil Cedex Ile-de-france France 91010
    50 Hopital Saint-Antoine Paris Cedex 12 Ile-de-france France 75012
    51 Hopital Necker-Enfants Malades Paris Ile-de-france France 75015
    52 Centre Hospitalier Universitaire de Toulouse Hopital Purpan Toulouse Midi-pyrenees France 31059
    53 Hopital Saint-Vincent de Paul - Lille Lille Cedex NORD Pas-de-calais France 59020
    54 Centre Hospitalier Regional Universitaire de Lille Lille Cedex NORD Pas-de-calais France 59037
    55 Centre Hospitalier Universitaire Nantes - Hotel Dieu Nantes Cedex 1 PAYS DE LA Loire France 44093
    56 Centre Hospitalier Universitaire de Poitiers Poitiers Poitou-charentes France 86000
    57 Universitatsklinik Tubingen Tuebingen Baden-wuerttemberg Germany 72076
    58 Universitatsklinikum Dusseldorf Duesseldorf Nordrhein-westfalen Germany 40225
    59 Universitatsklinikum Leipzig Leipzig Sachsen Germany 04103
    60 Universitatsklinikum Hamburg-Eppendorf Hamburg Germany 20251
    61 Evaggelismos General Hospital Athens Attica Greece 10676
    62 Alexandra General Hospital of Athens Athens Attica Greece 11528
    63 University Regional General Hospital of Patras Patra Peloponnese Greece 26504
    64 Cork University Hospital Cork Ireland T12 DC4A
    65 Saint Vincent's University Hospital Dublin Ireland D04 T6F4
    66 Mater Misericordiae University Hospital Dublin Ireland D07 R2WY
    67 The Chaim Sheba Medical Center Ramat Gan Tel Aviv Israel 52621
    68 Hadassah Medical Center Jerusalem Israel 9112001
    69 Tel Aviv Sourasky Medical Center Tel Aviv Israel 6423906
    70 Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona Ancona Italy 60126
    71 Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant'Orsola-Malpighi Bologna Italy 40138
    72 Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele Catania Italy 95125
    73 Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano Milano Italy 20133
    74 Fondazione IRCCS Policlinico San Matteo Pavia Italy 27100
    75 Nagoya City University Hospital Nagoya Aichi Japan 467-8601
    76 University Hospital - Kyoto Preferctural University of Medicine Kyoto-City Kyoto Japan 602-8566
    77 National Hospital Organization Okayama Medical Center Okayama-city Okayama Japan 701-1192
    78 Yamanashi Prefectural Central Hospital Chuo-shi Yamanasi Japan 409-3898
    79 Japanese Red Cross Medical Center Tokyo Japan 150-8935
    80 Chonnam National University Hwasun Hospital Hwasun Jeollanam-do Korea, Republic of 58128
    81 Seoul National University Hospital Seoul Korea, Republic of 03080
    82 The Catholic University of Korea - Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
    83 Oslo Universitetssykehus-Ulleval Hospital Oslo Norway 0450
    84 Ad-Vance Medical Research Ponce Puerto Rico 00730
    85 Hospital Espanol Auxilio Mutuo San Juan Puerto Rico 00919
    86 Hospital Universitari Germans Trias i Pujol Badalona Barcelona Spain 08916
    87 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    88 Hospital Clinic de Barcelona Barcelona Spain 08036
    89 Hospital Universitario 12 de Octubre Madrid Spain 28041
    90 Hospital Universitario Virgen de la Arrixaca Murcia Spain 30120
    91 Hospital Universitario de Salamanca Salamanca Spain 37007
    92 Hospital Universitario Marques de Valdecilla Santander Spain 39008
    93 Tri-Service General Hospital Taipei Taipei CITY Taiwan 11490
    94 National Taiwan University Hospital Taipei Taiwan 100
    95 Taipei Veterans General Hospital Taipei Taiwan 11217
    96 Ankara Universitesi Yenimahalle Ankara Turkey 06560
    97 Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi Üsküdar Istanbul Turkey 34664
    98 Ondokuz Mayis Universitesi Tp Fakultesi Samsun Turkey 55139
    99 University Hospitals Birmingham NHS Foundation Trust Birmingham England United Kingdom B9 5SS
    100 The Leeds Teaching Hospitals NHS Trust Leeds England United Kingdom LS9 7TF
    101 University College London Hospitals NHS Foundation Trust London England United Kingdom NW1 2BU
    102 King's College Hospital NHS Foundation Trust London England United Kingdom SE5 9RS
    103 Nottingham University Hospitals NHS Trust Nottingham England United Kingdom NG5 1PB
    104 Oxford University Hospitals NHS Foundation Trust Oxford England United Kingdom OX3 7LE
    105 The Royal Marsden NHS Foundation Trust Sutton England United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03215030
    Other Study ID Numbers:
    • TAK-573-1501
    • TV48573-ONC-10128
    • U1111-1195-8134
    • 2021-006038-37
    First Posted:
    Jul 12, 2017
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takeda
    Drug Therapy
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone

    Study Results

    No Results Posted as of Jul 15, 2022