Relapsed and/or Refractory Multiple Myeloma (RRMM)
Conditions
Keywords
Drug Therapy
Brief summary
TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies (mAbs) to treat participants who have relapsed or refractory multiple myeloma (RRMM). The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination with anti-CD38 (mAbs) and to determine the recommended Phase 2 dose (RP2D). Participants will be on this combination treatment for 28-day cycles. They will continue with this treatment until disease progression or unacceptable toxicity.
Detailed description
The drug being tested in this study is called TAK-981. TAK-981 in combination with an anti-CD38 monoclonal antibody (mAbs) is being tested to treat people who have RRMM. The study will include a dose escalation phase and a dose expansion phase. The study will enroll approximately 81 participants; approximately 30 participants in the dose escalation phase (Part 1) approximately 15 participants in (Part 2) and up to 36 participants in dose expansion phase (Part 2). Participants will receive escalating doses of TAK-981 in combination with fixed doses as follows: * Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab * Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab * Phase 1b, Part 2 - Dose Escalation: TAK-981 + Daratumumab and Hyaluronidase-fihj Once RP2D is determined in Phase 1, participants with RRMM will be enrolled in Phase 2. • Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab This multi-center trial will be conducted in North America. The overall time to participate in this study is 2 years. Participants will make multiple visits to the clinic, and progression-free survival follow-up for maximum up to 12 months after last dose of study drug.
Interventions
DRUGTAK-981
TAK-981 IV infusion.
DRUGMezagitamab
Mezagitamab SC injection.
Daratumumab and Hyaluronidase-fihj SC injection.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must have RRMM with measurable disease: a) Has measurable disease defined as one of the following: * Serum M-protein ≥0.5 g/dL (≥5 g/L). * Urine M-protein ≥200 mg/24 hours. * In participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum free light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100 mg/L), provided serum FLC ratio is abnormal. 2. Has undergone stem cell transplant or is considered transplant ineligible. 3. Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory, or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or pomalidomide \[thalidomide excluded\]), at least 1 proteasome inhibitor (ie, bortezomib, ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have demonstrated disease progression with the last therapy. 5.Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 6.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.
Exclusion criteria
1. Received treatment with systemic anticancer treatments within 14 days before the first dose of study drug. 2. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of the first dose of TAK-981 and throughout the duration of this trial. 3. Prior radiation therapy within 14 days of the first dose of TAK-981. 4. Major surgery within 4 weeks before C1D1. participants should be fully recovered from any surgically related complications. 5. Plasmapheresis within 28 days of randomization. 6. Diagnosis of primary amyloidosis, Waldenström's disease, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), myelodysplastic syndrome, or myeloproliferative syndrome. 7. With disease where the only measurable parameter is plasmacytoma. 8. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy. 9. Prior treatment with more than 1 anti-CD38 antibody. 10. Requires the use of drugs known to prolong the corrected QT interval (QTc) (during Phase 1b only). 11. History of QT interval with Fridericia's correction (QTcF) \>480 ms. 12. History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C infection. 13. Systemic infection requiring systemic antibiotic therapy. 14. Active or history pneumonitis. 15. Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study drug. 16. Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers. 17. History of unstable cardiac comorbidities in the following 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) | TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. |
| Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) | The severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. |
| Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | Cycle 1 (Cycle length = 28 Days) | DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (\>=) 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 greater than (\>) 14 days or missed \>1 planned doses of TAK-981/monoclonal antibody (mAb) in Cycle 1 due to TEAEs. |
| Phase 2: Overall Response Rate (ORR) | From date of treatment start to until date of first PD or death (whichever occurred first), up to 24 months | ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5 percent (%) plasma cells in bone marrow (BM). PR: \>50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by \>90% or to less than (\<) 200 milligrams per 24 hour (mg/24 h); If serum and urine M-protein were unmeasurable, \>50% decrease in difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | AUC0-inf for TAK-981 was reported. |
| Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | t1/2z for TAK-981 was reported. |
| Phase 1b, Part 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | CL for TAK-981 was reported. |
| Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | Vss for TAK-981 was reported. |
| Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Baseline up to 12 months | ADA positive was defined as participants who had confirmed positive ADA status in at least 1 post-baseline assessments. \>=5-fold in ADA titer was defined as increase in the ADA titer value post-baseline of at least 5-fold from the positive ADA titer value at baseline. |
| Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycles 1, 2, 3, 4, 6, 7 and 12: Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | Observed serum concentrations of mezagitumab was reported. |
| Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 12 months) | ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow (BM). PR: \>50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by \>90% or to less than (\<) 200 milligrams per 24 hour (mg/24 h); If the serum and urine M-protein were unmeasurable, \>50% decrease in the difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required. |
| Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | From first dose of study drug until PD or death, whichever occurred first (up to 12 months) | CBR: % of participants with response of at least stable disease (SD) for \>=3 months or better (stringent CR \[sCR\], immunophenotypic CR \[iCR\], molecular CR \[mCR\], CR, very good partial response \[VGPR\], PR, minimal response \[MR\] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, \<5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein+urine M-protein level \<100mg/24h. PR: \>50% reduction of serum M-protein and in 24h urinary M-protein by \>90% or to \<200mg/24h. MR: \>=25% but \<=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD. |
| Phase 1b, Part 1: Duration of Response (DOR) Based on IMWG Criteria | From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (up to 12 months) | DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BM. PR: \>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \<200 mg/24 h; If the serum and urine M-protein were unmeasurable, 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 are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required. DOR was calculated for those participants with a confirmed PR or CR. |
| Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | From first dose of study drug to the date of the first documentation of PD or death, whichever occurred first (up to 12 months) | TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of \>25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be \>0.5 grams per deciliter \[g/dL\]). b) Urine M-component and/or (the absolute increase must be \>200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 millimoles per liter \[mmol/L\]) that can be attributed solely to the plasma cell proliferative disorder. |
| Phases 1b, Part 1: Time to Next Treatment (TTNT) | From the date of first dose of study drug to the date of the first dose initiation of the next line of antineoplastic therapy (up to 12 months) | TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason. |
| Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | From the first dose of study drug to date of PD or death, whichever occurred first (up to 12 months) | PFS was 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. PD was defined as increase of \>25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be \>0.5 g/dL). b) Urine M-component and/or (the absolute increase must be \>200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. |
| Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Pre-dose, at end of infusion (EOI), 2, 4, 6, and 24 hours post-dose; Cycle 1 Days 8 and 15: Pre-dose and EOI; Cycle 2 Days 1 and 15: Pre-dose and EOI (Cycle length = 28 days) | Observed plasma concentration of TAK-981 was reported. |
| Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days) | Blood samples were collected to assess TAK-981-SUMO adduct formation. TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981. |
| Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days) | Blood samples were collected to assess SUMO inhibition. SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains. |
| Phase 2: Number of Participants With TEAEs and TEAEs by Severity | Up to 24 months | TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. The severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. |
| Phase 2: CBR Based on IMWG Criteria | Up to 24 months | CBR: percentage of participants with response of at least (SD for \>=3 months or better sCR, iCR, mCR, CR, very good partial response \[VGPR\], PR, minimal response \[MR\] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, \<5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein+urine M-protein level \<100mg/24h. PR: \>50% reduction of serum M-protein and in 24h urinary M-protein by \>90% or to \<200mg/24h. MR:\>=25% but \<=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD. |
| Phase 2: DOR Based on IMWG Criteria | Up to 24 months | DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BM. PR: \>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \<200 mg/24 h; If the serum and urine M-protein were unmeasurable, 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 are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required. |
| Phase 2: TTP Based on IMWG Criteria | Up to 24 months | TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of \>25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be \>0.5 grams per deciliter \[g/dL\]). b) Urine M-component and/or (the absolute increase must be \>200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. |
| Phase 2: Time to Next Treatment (TTNT) | Up to 24 months | TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason. |
| Phase 2: PFS Based on IMWG Criteria | Up to 24 months | PFS was 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. PD was defined as increase of \>25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be \>0.5 g/dL). b) Urine M-component and/or (the absolute increase must be \>200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. |
| Phase 2: Overall Survival (OS) | Up to 24 months | OS was defined as the time from the date of first dose to the date of death. |
| Phase 2: Percentage of Participants With MRD Negative Status as Determined by Next-Generation Sequencing (NGS) | Up to 24 months | — |
| Phase 2: Minimal Residual Disease (MRD) Negative Rate | Up to 12 months | — |
| Phase 2: Durable MRD Negative Rate | Up to 12 months | — |
| Phases 1b, Part 1: Overall Survival (OS) | From date of first dose of study drug up to death from any cause (up to 27 months) | OS was defined as the time from the date of first dose to the date of death. OS was analyzed using Kaplan-Meier (KM) method. Participants were followed for survival after the last dose of study drug. |
| Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | Cmax for TAK-981 was reported. |
| Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | Tmax for TAK-981 was reported. |
| Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) | AUC0-t for TAK-981 was reported. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part in the study at 10 investigative sites in the United States and Canada from 20 April 2021 to 09 November 2023. Participants with diagnosis of Relapsed and/or Refractory Multiple Myeloma (RRMM) were enrolled in Phase 1b Part 1 to receive TAK-981 in combination with mezagitamab.
Pre-assignment details
This study consisted of Phase 1b and 2. Phase 1b (Dose Escalation) had two parts (Parts 1 and 2) and Phase 2 (Dose Expansion) was single part. Phase 1b- Part 2 and Phase 2 were not conducted, as study was terminated early after completion of Phase 1b Part 1 due to business reasons and therefore, no data for Phase 1b Part 2 and Phase 2 was collected and reported.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg Participants received TAK-981 60 mg, infusion, intravenously, twice weekly on Days 1, 4, 8, 11 and 15, and mezagitamab 600 mg, injection, subcutaneously, once weekly on Days 1, 8, 15 and 22 during Cycles 1 and 2, then once every 2 weeks during Cycles 3 through 6, further once every 4 weeks, until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. | 3 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg Participants received TAK-981 90 mg, infusion, intravenously, twice weekly on Days 1, 4, 8, 11 and 15, and mezagitamab 600 mg, injection, subcutaneously, once weekly on Days 1, 8, 15 and 22 during Cycles 1 and 2, then once every 2 weeks during Cycles 3 through 6, further once every 4 weeks, until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. | 3 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg Participants received TAK-981 90 mg, infusion, intravenously, in combination with mezagitamab 600 mg, injection, subcutaneously, once weekly on Days 1, 8, 15, 22 during Cycles 1 and 2, then every 2 weeks during Cycles 3 through 6, further once every 4 weeks until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. | 10 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg Participants received TAK-981 120 mg, infusion, intravenously, twice weekly on Days 1, 4, 8, 11 and 15, and mezagitamab 600 mg, injection, subcutaneously, once weekly on Days 1, 8, 15 and 22 during Cycles 1 and 2, then once every 2 weeks during Cycles 3 through 6, further once every 4 weeks, until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. | 3 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg Participants received TAK-981 120 mg, infusion, intravenously, in combination with mezagitamab 600 mg, injection, subcutaneously, once weekly on Days 1, 8, 15, 22 during Cycles 1 and 2, then every 2 weeks during Cycles 3 through 6, further once every 4 weeks until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. | 8 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 4 | 1 | 4 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 2 | 1 | 4 | 0 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 19.29 | 65.0 years STANDARD_DEVIATION 4.58 | 66.2 years STANDARD_DEVIATION 12.97 | 74.0 years STANDARD_DEVIATION 4 | 71.9 years STANDARD_DEVIATION 3.94 | 68.0 years STANDARD_DEVIATION 10.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 10 Participants | 2 Participants | 8 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 4 / 10 | 1 / 3 | 4 / 8 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 10 / 10 | 3 / 3 | 8 / 8 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 4 / 10 | 1 / 3 | 3 / 8 |
Outcome results
Primary
Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0
DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (\>=) 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 greater than (\>) 14 days or missed \>1 planned doses of TAK-981/monoclonal antibody (mAb) in Cycle 1 due to TEAEs.
Time frame: Cycle 1 (Cycle length = 28 Days)
Population: DLT-evaluable analysis set included participants who received at least 75 precent (%) of planned TAK-981 doses, all mAb doses, and have completed Cycle 1 procedures, or experienced a DLT in Cycle 1 in the phase 1 portion of the trial.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | 1 Participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | 1 Participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Based on NCI CTCAE Version 5.0 | 1 Participants |
Primary
Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs
The severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs 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 of study drug (up to 13 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | 7 Participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Grade 3 or Higher TEAEs | 7 Participants |
Primary
Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 10 Participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
Primary
Phase 2: Overall Response Rate (ORR)
ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5 percent (%) plasma cells in bone marrow (BM). PR: \>50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by \>90% or to less than (\<) 200 milligrams per 24 hour (mg/24 h); If serum and urine M-protein were unmeasurable, \>50% decrease in difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From date of treatment start to until date of first PD or death (whichever occurred first), up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981
AUC0-inf for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | 839 h*ng/mL | Geometric Coefficient of Variation 32.5 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | 1590 h*ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | 1590 h*ng/mL | Geometric Coefficient of Variation 36.1 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | 2180 h*ng/mL | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | 1690 h*ng/mL | Geometric Coefficient of Variation 22.2 |
Secondary
Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981
AUC0-t for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | 813 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30.4 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | 1550 hours*nanogram per milliliter (h*ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | 1590 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33.9 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | 2120 hours*nanogram per milliliter (h*ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-981 | 1690 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.8 |
Secondary
Phase 1b, Part 1, CL: Total Clearance for TAK-981
CL for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | 71.5 liters per hour (L/h) | Geometric Coefficient of Variation 32.5 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | 56.5 liters per hour (L/h) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | 56.7 liters per hour (L/h) | Geometric Coefficient of Variation 36.1 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | 55.0 liters per hour (L/h) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | 71.2 liters per hour (L/h) | Geometric Coefficient of Variation 22.2 |
Secondary
Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981
Cmax for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | 225 ng/mL | Geometric Coefficient of Variation 44.3 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | 642 ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | 617 ng/mL | Geometric Coefficient of Variation 61.7 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | 1120 ng/mL | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | 842 ng/mL | Geometric Coefficient of Variation 27.5 |
Secondary
Phase 1b, Part 1: Duration of Response (DOR) Based on IMWG Criteria
DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BM. PR: \>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \<200 mg/24 h; If the serum and urine M-protein were unmeasurable, 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 are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required. DOR was calculated for those participants with a confirmed PR or CR.
Time frame: From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (up to 12 months)
Population: Response-evaluable analysis set included participants with measurable disease at baseline and at least 1 posttreatment evaluation. Here, 'overall number of participants analyzed' signifies participants who had CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Duration of Response (DOR) Based on IMWG Criteria | 3.2 months |
Secondary
Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer
ADA positive was defined as participants who had confirmed positive ADA status in at least 1 post-baseline assessments. \>=5-fold in ADA titer was defined as increase in the ADA titer value post-baseline of at least 5-fold from the positive ADA titer value at baseline.
Time frame: Baseline up to 12 months
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with Positive ADA | 0 Participants |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with >=5-fold in ADA titer | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with Positive ADA | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with >=5-fold in ADA titer | 0 Participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with Positive ADA | 2 Participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with >=5-fold in ADA titer | 0 Participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with >=5-fold in ADA titer | 0 Participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with Positive ADA | 0 Participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with Positive ADA | 0 Participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Number of Participants With Positive Anti-drug Antibodies (ADA) for TAK-981 + Mezagitamab and >= 5-fold in ADA Titer | Participants with >=5-fold in ADA titer | 0 Participants |
Secondary
Phase 1b, Part 1: Observed Plasma Concentration of TAK-981
Observed plasma concentration of TAK-981 was reported.
Time frame: Cycle 1 Day 1: Pre-dose, at end of infusion (EOI), 2, 4, 6, and 24 hours post-dose; Cycle 1 Days 8 and 15: Pre-dose and EOI; Cycle 2 Days 1 and 15: Pre-dose and EOI (Cycle length = 28 days)
Population: Pharmacokinetic (PK) analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here number analyzed signifies participants evaluable at specified time-point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: Predose | 0.177 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.8 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: EOI | 318 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 84.6 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: EOI | 225 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.3 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: Predose | 0.182 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.9 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 2 hours | 79.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.7 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: EOI | 212 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 13.1 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 4 hours | 37.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.7 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: EOI | 191 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 6 hours | 31.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 65.4 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 24 hours | 3.27 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.3 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: EOI | 281 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.1 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: EOI | 585 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.8 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: Predose | 0.519 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.6 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: Predose | 0.536 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: EOI | 576 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17.1 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 24 hours | 5.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 12.9 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: EOI | 642 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 4 hours | 63.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37.3 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: EOI | 844 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.5 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 6 hours | 33.2 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 2 hours | 110 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.8 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: Predose | 0.758 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 1139.8 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 24 hours | 4.75 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: EOI | 617 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61.7 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 2 hours | 115 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.3 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 4 hours | 69.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.3 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: EOI | 829 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.7 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: EOI | 812 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55.5 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: EOI | 767 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61.6 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: EOI | 634 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.3 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 24 hours | 5.51 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.2 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: EOI | 830 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 4 hours | 63.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.9 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 2 hours | 139 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.9 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: EOI | 1580 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: EOI | 1120 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: Predose | 0.411 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.8 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: EOI | 1500 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: EOI | 1360 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.1 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: Predose | 0.286 nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: EOI | 842 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.5 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: EOI | 820 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 8.7 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 4 hours | 56.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.9 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 15: EOI | 713 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 14.2 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 15: EOI | 940 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.6 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 24 hours | 6.29 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.7 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: 2 hours | 116 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.3 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 8: EOI | 1070 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.4 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 1 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Cycle 2 Day 1: Predose | NA nanograms per milliliter (ng/mL) | — |
Secondary
Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria
ORR: percentage of participants who achieve complete response (CR) or partial response (PR) or better per investigator assessment by IMWG.CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow (BM). PR: \>50 percent (%) reduction of serum M-protein and reduction in 24 hours (h) urinary M-protein by \>90% or to less than (\<) 200 milligrams per 24 hour (mg/24 h); If the serum and urine M-protein were unmeasurable, \>50% decrease in the difference between involved and uninvolved free light chain (FLC) levels was required in place of M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 12 months)
Population: Response-evaluable analysis set included participants with measurable disease at baseline and at least 1 posttreatment evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | 0.0 percentage of participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | 0.0 percentage of participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | 0.0 percentage of participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | 0.0 percentage of participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: ORR Based on International Myeloma Working Group (IMWG) Criteria | 16.7 percentage of participants |
Secondary
Phase 1b, Part 1: Serum Concentration of Mezagitamab
Observed serum concentrations of mezagitumab was reported.
Time frame: Cycles 1, 2, 3, 4, 6, 7 and 12: Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. Here number analyzed signifies participants evaluable at specified time-point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 2 Day 1 | 99400 ng/mL | Geometric Coefficient of Variation 38.1 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 4 Day 1 | 94500 ng/mL | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 6 Day 1 | 38400 ng/mL | Geometric Coefficient of Variation 83.9 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 1 Day 1 | NA ng/mL | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 3 Day 1 | 95500 ng/mL | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 7 Day 1 | 71900 ng/mL | — |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 12 Day 1 | NA ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 6 Day 1 | 27000 ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 1 Day 1 | NA ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 3 Day 1 | 200000 ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 2 Day 1 | 103000 ng/mL | Geometric Coefficient of Variation 50.9 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 3 Day 1 | 68400 ng/mL | Geometric Coefficient of Variation 337.7 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 6 Day 1 | 101000 ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 1 Day 1 | NA ng/mL | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 2 Day 1 | 81800 ng/mL | Geometric Coefficient of Variation 53.3 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 1 Day 1 | NA ng/mL | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 2 Day 1 | 64900 ng/mL | Geometric Coefficient of Variation 59.4 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 3 Day 1 | 146000 ng/mL | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 3 Day 1 | 154000 ng/mL | Geometric Coefficient of Variation 94.7 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 6 Day 1 | 117000 ng/mL | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 2 Day 1 | 29000 ng/mL | Geometric Coefficient of Variation 6634 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Cycle 1 Day 1 | NA ng/mL | — |
Secondary
Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981
t1/2z for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | 5.24 hours |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | 5.25 hours |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | 4.96 hours |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | 5.33 hours |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | 5.49 hours |
Secondary
Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
Tmax for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | 0.97 hours |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | 1.12 hours |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | 1.09 hours |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | 1.09 hours |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | 1.15 hours |
Secondary
Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981
Vss for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days)
Population: PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | 377 liters | Geometric Coefficient of Variation 5.1 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | 281 liters | — |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | 250 liters | Geometric Coefficient of Variation 49 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | 259 liters | — |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | 331 liters | Geometric Coefficient of Variation 20.4 |
Secondary
Phase 2: CBR Based on IMWG Criteria
CBR: percentage of participants with response of at least (SD for \>=3 months or better sCR, iCR, mCR, CR, very good partial response \[VGPR\], PR, minimal response \[MR\] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, \<5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein+urine M-protein level \<100mg/24h. PR: \>50% reduction of serum M-protein and in 24h urinary M-protein by \>90% or to \<200mg/24h. MR:\>=25% but \<=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: DOR Based on IMWG Criteria
DOR was defined as a time from date of first documentation of a PR or better to the date of first documentation of PD based on IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BM. PR: \>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \<200 mg/24 h; If the serum and urine M-protein were unmeasurable, 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 are not measurable, and serum free light assay was also not measurable, \>50% reduction in plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was \>30%. In addition to the above listed criteria, if present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Durable MRD Negative Rate
Time frame: Up to 12 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Minimal Residual Disease (MRD) Negative Rate
Time frame: Up to 12 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Number of Participants With TEAEs and TEAEs by Severity
TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. The severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs 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: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Overall Survival (OS)
OS was defined as the time from the date of first dose to the date of death.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Percentage of Participants With MRD Negative Status as Determined by Next-Generation Sequencing (NGS)
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: PFS Based on IMWG Criteria
PFS was 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. PD was defined as increase of \>25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be \>0.5 g/dL). b) Urine M-component and/or (the absolute increase must be \>200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: Time to Next Treatment (TTNT)
TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phase 2: TTP Based on IMWG Criteria
TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of \>25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be \>0.5 grams per deciliter \[g/dL\]). b) Urine M-component and/or (the absolute increase must be \>200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time frame: Up to 24 months
Population: The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 2 part of the study. Hence, the data for this outcome measure could not collected, analyzed and reported.
Secondary
Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria
CBR: % of participants with response of at least stable disease (SD) for \>=3 months or better (stringent CR \[sCR\], immunophenotypic CR \[iCR\], molecular CR \[mCR\], CR, very good partial response \[VGPR\], PR, minimal response \[MR\] or SD) per investigator assessment by IMWG. sCR: CR plus normal FLC ratio, absence of clonal cells in BM. iCR: sCR plus absence of phenotypical aberrant plasma in BM with minimum of 1 million total BM cells. mCR: CR plus negative allele-specific oligonucleotide polymerase chain reaction. CR: Negative immunofixation on serum, urine, disappearance soft tissue plasmacytomas, \<5% plasma cells in BM. VGPR: Serum, urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein+urine M-protein level \<100mg/24h. PR: \>50% reduction of serum M-protein and in 24h urinary M-protein by \>90% or to \<200mg/24h. MR: \>=25% but \<=49% reduction in serum M-protein, reduction in 24h urine M-protein by 50 to 89%. SD: No CR, VGPR, PR or PD.
Time frame: From first dose of study drug until PD or death, whichever occurred first (up to 12 months)
Population: Response-evaluable analysis set included participants with measurable disease at baseline and at least 1 posttreatment evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | 66.7 percentage of participants |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | 33.3 percentage of participants |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | 11.1 percentage of participants |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | 0.0 percentage of participants |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Clinical Benefit Rate (CBR) Based on IMWG Criteria | 33.3 percentage of participants |
Secondary
Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes
Blood samples were collected to assess TAK-981-SUMO adduct formation. TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981.
Time frame: Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days)
Population: Pharmacodynamic analysis set included participants who provided evaluable blood samples (Cycle 1 Day 1 predose sample and at least 1 postdose sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and here, number analyzed signifies participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 2.4 fold change | Standard Deviation 1.12 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 4.3 fold change | Standard Deviation 0.81 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 3.5 fold change | Standard Deviation 0.03 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.6 fold change | Standard Deviation 0.01 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 4.0 fold change | Standard Deviation 1.18 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.3 fold change | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 3.8 fold change | Standard Deviation 0.65 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.5 fold change | Standard Deviation 0.3 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 5.1 fold change | Standard Deviation 1 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 6.0 fold change | Standard Deviation 2.83 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.8 fold change | Standard Deviation 0.78 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 2.2 fold change | Standard Deviation 0.62 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 3.7 fold change | Standard Deviation 1.47 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 1.4 fold change | Standard Deviation 0.61 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 3.9 fold change | Standard Deviation 2.63 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 4.1 fold change | Standard Deviation 0.35 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 3.5 fold change | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 5.7 fold change | Standard Deviation 2.11 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 2.8 fold change | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.4 fold change | Standard Deviation 0.07 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.0 fold change | Standard Deviation 0.14 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 2.3 fold change | Standard Deviation 0.89 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 6.1 fold change | Standard Deviation 4.14 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.1 fold change | Standard Deviation 1.06 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 4.4 fold change | Standard Deviation 1.6 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.2 fold change | Standard Deviation 0.39 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in Level of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 5.6 fold change | Standard Deviation 1.12 |
Secondary
Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes
Blood samples were collected to assess SUMO inhibition. SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains.
Time frame: Cycle 1 Day 1: 1, 4, and 24 hours post-dose; Cycle 1 Day 8: Pre-dose, and 1 hour post-dose; Cycle 1 Day 15: Pre-dose (Cycle length = 28 days)
Population: Pharmacodynamic analysis set included participants who provided evaluable blood samples (Cycle 1 Day 1 predose sample and at least 1 postdose sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and here, number analyzed signifies participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 0.7 fold change | Standard Deviation 0.08 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.8 fold change | Standard Deviation 0.14 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.4 fold change | Standard Deviation 0.25 |
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 0.6 fold change | Standard Deviation 0.42 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.3 fold change | Standard Deviation 0.19 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | — |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 0.6 fold change | Standard Deviation 0.01 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 0.6 fold change | Standard Deviation 0.24 |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.08 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.61 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 0.8 fold change | Standard Deviation 0.23 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 0.7 fold change | Standard Deviation 0.2 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.29 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 0.5 fold change | Standard Deviation 0.39 |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.7 fold change | Standard Deviation 0.3 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.4 fold change | Standard Deviation 0.29 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 0.8 fold change | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.16 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 0.8 fold change | — |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 0.6 fold change | Standard Deviation 0.58 |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.9 fold change | Standard Deviation 0.03 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 15: Pre-dose | 4.0 fold change | Standard Deviation 5.38 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 1.3 fold change | Standard Deviation 1.51 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.7 fold change | Standard Deviation 0.3 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 1: 24 hour post-dose | 1.6 fold change | Standard Deviation 1.85 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.5 fold change | Standard Deviation 1.09 |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Fold Change From Baseline in SUMO Pathway Inhibition in Peripheral Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 1.3 fold change | Standard Deviation 1.56 |
Secondary
Phases 1b, Part 1: Overall Survival (OS)
OS was defined as the time from the date of first dose to the date of death. OS was analyzed using Kaplan-Meier (KM) method. Participants were followed for survival after the last dose of study drug.
Time frame: From date of first dose of study drug up to death from any cause (up to 27 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Overall Survival (OS) | NA months |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Overall Survival (OS) | NA months |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Overall Survival (OS) | 13.8 months |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Overall Survival (OS) | 10.3 months |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Overall Survival (OS) | 11.0 months |
Secondary
Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria
PFS was 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. PD was defined as increase of \>25% from lowest response value in any one or more of the following: a) Serum M-component and/or (the absolute increase must be \>0.5 g/dL). b) Urine M-component and/or (the absolute increase must be \>200 mg/24h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL. d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time frame: From the first dose of study drug to date of PD or death, whichever occurred first (up to 12 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | 7.9 months |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | 1.0 months |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | 1.2 months |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | 1.6 months |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Progression-free Survival (PFS) Based on IMWG Criteria | 3.7 months |
Secondary
Phases 1b, Part 1: Time to Next Treatment (TTNT)
TTNT was defined as the time from the date of first dose to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.
Time frame: From the date of first dose of study drug to the date of the first dose initiation of the next line of antineoplastic therapy (up to 12 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Next Treatment (TTNT) | 10.6 months |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Next Treatment (TTNT) | 5.2 months |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Next Treatment (TTNT) | 1.6 months |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Next Treatment (TTNT) | NA months |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Next Treatment (TTNT) | 6.3 months |
Secondary
Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria
TTP: time from date of first dose to date of first documentation of PD as defined by standard disease criteria. PD was defined as increase of \>25% from lowest response value in any one or more of following: a) Serum M-component and/or (the absolute increase must be \>0.5 grams per deciliter \[g/dL\]). b) Urine M-component and/or (the absolute increase must be \>200 mg/24 h). c) Only in participants without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 milligrams per deciliter (mg/dL). d) Bone marrow plasma cell percentage; the absolute percentage must be \>10%. e) Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. f) Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 millimoles per liter \[mmol/L\]) that can be attributed solely to the plasma cell proliferative disorder.
Time frame: From first dose of study drug to the date of the first documentation of PD or death, whichever occurred first (up to 12 months)
Population: Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | 7.9 months |
| Phase 1b, Part 1: TAK-981 90 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | 1.0 months |
| Phase 1b, Part 1: TAK-981 90 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | 1.2 months |
| Phase 1b, Part 1: TAK-981 120 mg BIW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | 1.6 months |
| Phase 1b, Part 1: TAK-981 120 mg QW + Mezagitamab 600 mg | Phases 1b, Part 1: Time to Progression (TTP) Based on IMWG Criteria | 3.7 months |