Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Phase 1b: Number of Participants with Treatment Emergent Adverse Events (TEAEs), By Severity at Each Dose Level |
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death. |
Up to 24 months |
|
| Primary |
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) |
DLT will be defined by NCI CTCAE, 5.0, Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade =3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 anemia or thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities leading to dose reduction/discontinuation. Delay in Cycle 2 by >14 days or missed >1 planned doses of TAK-981/mAb in Cycle 1 due to TEAEs. |
Through Cycle 1 (Each cycle is of 28 days) |
|
| Primary |
Phase 2: Overall Response Rate (ORR) (Response of Atleast Partial Response [PR]) as Assessed by the Investigator's Based on International Myeloma Working Group (IMWG) Criteria |
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) or better during the study as assessed by International Myeloma Working Group (IMWG) criteria. |
Up to 24 months |
|
| Secondary |
Cmax: Maximum Observed Plasma Concentration for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
AUC8: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
t1/2z: Terminal Disposition Phase Half-life for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
CL: Total Clearance After Intravenous Administration for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 |
|
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
Number of Participants with Anti-mezagitamab or anti-daratumumab antibody (ADA) |
|
Up to 24 months |
|
| Secondary |
Serum Sparse Concentration of Mezagitamab or Daratumumab |
Serum concentrations of mezagitumab and daratumumab will be evaluated during the study. |
Cycles 1 and 2 (cycle = 28 days), on multiple days and at multiple timepoints (Up to 24 hours) post dose |
|
| Secondary |
Phase 1b: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation |
TAK-981-SUMO adduct formation in blood will be evaluated. |
Up to 24 months |
|
| Secondary |
Phase 2: Number of Participants with TEAEs by Severity |
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity grade will be evaluated as per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. TEAEs will be graded on a 5-point scale where 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life-threatening and 5 = death. |
Up to 24 months |
|
| Secondary |
Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator's Based on IMWG Criteria |
ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) or better (determined by the investigator) during the study as assessed by IMWG criteria. |
Up to 24 months |
|
| Secondary |
Phases 1b and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator's Based on IMWG Criteria |
CBR is defined as percentage of participants who achieve at least a stable disease for a least 3 months or better. |
Up to 24 months |
|
| Secondary |
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator's Based on IMWG Criteria |
DOR is defined as a time from the time of first documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study as assessed by the investigator. |
Up to 24 months |
|
| Secondary |
Phases 1b and 2: Time to Progression (TTP) as Assessed by the Investigator's Based on IMWG Criteria |
TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression as assessed by the investigator. |
Up to 24 months |
|
| Secondary |
Phases 1b and 2: Time to Next Treatment (TTNT) as Assessed by the Investigator's Based on IMWG Criteria |
TTNT is defined as the time from the date of first dose of study drug to the date of the first dose of initiation of the next line of antineoplastic therapy, for any reason as assessed by the investigator. |
Up to 24 months |
|
| Secondary |
Phases 1b and 2: Progression-free Survival (PFS) as Assessed by the Investigator's Based on IMWG Criteria |
PFS is defined as time from the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study as assessed by the investigator. |
Up to 24 months |
|
| Secondary |
Phases 1b and 2: Overall Survival (OS) as Assessed by the Investigator Based on IMWG Criteria |
OS is defined as the time from the date of enrollment to the date of death as assessed by the investigator. |
Up to 24 months |
|
| Secondary |
Phase 2: Percentage of Participants with MRD Negative Rate |
MRD negativity is defined as the absence of MRD. MRD negativity rate is defined as percentage of participants who have achieved MRD negative status at 1 year. |
Up to 1 year |
|
| Secondary |
Phase 2: Percentage of Participants with Minimal Residual Disease (MRD) Negative Status As Determined By Next-Generation Sequencing (NGS) |
MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between as determined by NGS. |
Up to 24 months |
|
| Secondary |
Phase 2: Number of Participants with Durable MRD Negative Rate |
Durable MRD negative rate is defined as the number of participants who have achieved MRD negative status (at 10^-5) at 2 bone marrow aspirates examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between. |
Up to 24 months |
|
