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Trial record 1 of 1 for:    TAK-573-1501
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A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03215030
Recruitment Status : Recruiting
First Posted : July 12, 2017
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda

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
Multiple Myeloma Drug: Modakafusp alfa Drug: Dexamethasone 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : October 4, 2017
Estimated Primary Completion Date : May 25, 2023
Estimated Study Completion Date : April 23, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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




Primary Outcome Measures :
  1. Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 90 months ]
  7. Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions [ Time Frame: Up to approximately 90 months ]
  8. Part 1: Percentage of Participants With Dose Modifications: Dose Reductions [ Time Frame: Up to approximately 90 months ]
  9. Part 1: Percentage of Participants With Clinically Significant Laboratory Values [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Up to approximately 90 months ]
  11. Part 1: Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to approximately 90 months ]
  18. Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  19. Part 2: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa [ Time Frame: 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 [ Time Frame: Up to approximately 90 months ]
  21. Part 2: λz: Terminal Disposition Rate Constant for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  22. Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  23. Part 2: CL: Clearance for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  24. Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  25. Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa [ Time Frame: Up to approximately 90 months ]
  26. Part 3: Objective Response Rate (ORR) by Investigator Assessment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 90 months ]
  39. Part 3: Percentage of Participants With Neutralizing Antibodies (NAb) [ Time Frame: Up to approximately 90 months ]
  40. Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter [ Time Frame: 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) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

    1. Serum M-protein ≥500 mg/dL (≥5 g/L)
    2. Urine M-protein ≥200 mg/24 hours.
    3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
  3. 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.
  4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03215030


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
Show Show 103 study locations
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03215030    
Other Study ID Numbers: TAK-573-1501
TV48573-ONC-10128 ( Other Identifier: Former Id )
U1111-1195-8134 ( Registry Identifier: WHO )
2021-006038-37 ( EudraCT Number )
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
URL: https://vivli.org/ourmember/takeda/

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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:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents