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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab | Experimental | Mezagitamab: A fixed dose of 600 mg subcutaneous (SC) injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks in Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 BIW intravenous (IV) infusion on Days 1, 4, 8, 11 and 15 in Cycle 1 and 2 (each Cycle is of 28 days) followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. |
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| Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab | Experimental | Mezagitamab: A fixed dose of 600 mg SC injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks from Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: Escalating doses of TAK-981 QW IV infusion on Days 1, 8, 15, and 22 in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks. up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. |
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| Phase 1b, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihj | Experimental | Daratumumab and hyaluronidase-fihj: 1800 mg SC injection QW once weekly in Cycles 1 and 2 , (each cycle is of 28 days) followed by every 2 weeks in Cycle 3 through 6 , followed by every 4 weeks up to Cycle 24 until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. TAK-981: As per dose and schedule of TAK-981 defined in Phase 1b Part 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-981 | Drug | TAK-981 IV infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) |
| 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. | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) |
| 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. | Cycle 1 (Cycle length = 28 Days) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Observed plasma concentration of TAK-981 was reported. | 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) |
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Inclusion Criteria:
Participants must have RRMM with measurable disease:
a) Has measurable disease defined as one of the following:
Has undergone stem cell transplant or is considered transplant ineligible.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Arizona - PPDS | Scottsdale | Arizona | 85259 | United States | ||
| Mayo Clinic Jacksonville - PPDS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35226739 | Derived | Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267. |
| Label | URL |
|---|---|
| Related Info | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b, Part 1: TAK-981 60 mg BIW + Mezagitamab 600 mg | Participants received TAK-981 60 milligrams (mg), infusion, intravenously, twice weekly (BIW) 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 30, 2021 | Jul 30, 2024 |
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| Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab | Experimental | TAK-981 at RP2D as determined in Phase 1b. Mezagitamab at a fixed dose of 600 mg SC injection or Daratumumab and Hyaluronidase-fihj at a fixed dose of 1800 mg weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycle 3 through 6, followed by every 4 weeks up to Cycle 24 or until disease progression unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. |
|
| Mezagitamab | Drug | Mezagitamab SC injection. |
|
| Daratumumab and Hyaluronidase-fihj | Drug | Daratumumab and Hyaluronidase-fihj SC injection. |
|
| 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. | From date of treatment start to until date of first PD or death (whichever occurred first), up to 24 months |
| Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 |
Cmax for TAK-981 was reported. |
| Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | Tmax for TAK-981 was reported. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| 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. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| 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. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | t1/2z for TAK-981 was reported. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| Phase 1b, Part 1, CL: Total Clearance for TAK-981 | CL for TAK-981 was reported. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | Vss for TAK-981 was reported. | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
| 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. | Baseline up to 12 months |
| Phase 1b, Part 1: Serum Concentration of Mezagitamab | Observed serum concentrations of mezagitumab was reported. | 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) |
| 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. | From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 12 months) |
| 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. | From first dose of study drug until PD or death, whichever occurred first (up to 12 months) |
| 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. | From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (up to 12 months) |
| 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. | From first dose of study drug to the date of the first documentation of PD or death, whichever occurred first (up to 12 months) |
| 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. | 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) |
| 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. | From the first dose of study drug to date of PD or death, whichever occurred first (up to 12 months) |
| 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. | From date of first dose of study drug up to death from any cause (up to 27 months) |
| 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. | 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) |
| 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. | 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) |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| Phase 2: Overall Survival (OS) | OS was defined as the time from the date of first dose to the date of death. | Up to 24 months |
| 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 |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Winship Cancer Institute, Emory University | Atlanta | Georgia | 30322-1013 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| American Oncology Partners of Maryland, PA | Bethesda | Maryland | 20817 | United States |
| Mayo Clinic - Cancer Center - Rochester - PPDS | Rochester | Minnesota | 55905 | United States |
| Oncology Hematology West (Omaha) - USOR | Omaha | Nebraska | 68130 | United States |
| Weill Cornell Medical Center | New York | New York | 10065 | United States |
| TriHealth Cancer Institute | Cincinnati | Ohio | 45220 | United States |
| Baylor Sammons Cancer Center | Dallas | Texas | 75246 | United States |
| Northeast Texas Cancer and Research Institute | Tyler | Texas | 75702 | United States |
| Medical College of Wisconsin Cancer Center | Milwaukee | Wisconsin | 53226 | United States |
| Hopital Maisonneuve-Rosemont | Montreal | Quebec | H1T 2M4 | Canada |
| FG001 | 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. |
| FG002 | 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 (QW) 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | Phase 1b, Part 2: TAK-981 + Daratumumab + Hyaluronidase-fihj | Participants were planned to receive TAK-981, infusion, intravenously, in combination with daratumumab and hyaluronidase-fihj, injection, subcutaneously, once weekly in 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. No participants were enrolled in this arm as this study was terminated early before start of enrolment in Phase 1b, Part 2. |
| FG006 | Phase 2: TAK-981 (RP2D) + Selected Anti-CD38 Antibody | Participants were planned to receive TAK-981 recommended phase 2 dose (RP2D), infusion, intravenously, in combination with an anti-CD38 antibody (mezagitamab or daratumumab and hyaluronidase-fihj), injection, subcutaneously, for up to 24 cycles or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first. Each Cycle length was 28 days. No participants were enrolled in this arm as this study was terminated early before start of enrolment in Phase 2. |
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Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Count of Participants | Participants | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Count of Participants | Participants | From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months) |
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| 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. | 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. | Posted | Count of Participants | Participants | Cycle 1 (Cycle length = 28 Days) |
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| 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. | 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. | Posted | From date of treatment start to until date of first PD or death (whichever occurred first), up to 24 months |
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| Secondary | Phase 1b, Part 1: Observed Plasma Concentration of TAK-981 | Observed plasma concentration of TAK-981 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 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) |
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| Secondary | Phase 1b, Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cmax for TAK-981 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| Secondary | Phase 1b, Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 | Tmax for TAK-981 was reported. | 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. | Posted | Median | Full Range | hours | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanogram per milliliter (h*ng/mL) | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| Secondary | Phase 1b, Part 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | t1/2z for TAK-981 was reported. | 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. | Posted | Median | Full Range | hours | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| Secondary | Phase 1b, Part 1, CL: Total Clearance for TAK-981 | CL for TAK-981 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour (L/h) | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| Secondary | Phase 1b, Part 1, Vss: Volume of Distribution at Steady State for TAK-981 | Vss for TAK-981 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 28 days) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Count of Participants | Participants | Baseline up to 12 months |
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| Secondary | Phase 1b, Part 1: Serum Concentration of Mezagitamab | Observed serum concentrations of mezagitumab was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| 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. | Response-evaluable analysis set included participants with measurable disease at baseline and at least 1 posttreatment evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 12 months) |
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| 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. | Response-evaluable analysis set included participants with measurable disease at baseline and at least 1 posttreatment evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose of study drug until PD or death, whichever occurred first (up to 12 months) |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | months | From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (up to 12 months) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Median | 95% Confidence Interval | months | From first dose of study drug to the date of the first documentation of PD or death, whichever occurred first (up to 12 months) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Median | 95% Confidence Interval | months | 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) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Median | 95% Confidence Interval | months | From the first dose of study drug to date of PD or death, whichever occurred first (up to 12 months) |
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| 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. | Safety analysis set included participants who received at least 1 dose, even if incomplete, of study drug. | Posted | Median | 95% Confidence Interval | months | From date of first dose of study drug up to death from any cause (up to 27 months) |
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| 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. | 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. | Posted | Mean | Standard Deviation | fold change | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | fold change | 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) |
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| 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. | 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. | Posted | Up to 24 months |
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| 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. | 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. | Posted | Up to 24 months |
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| 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. | 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. | Posted | Up to 24 months |
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| 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. | 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. | Posted | Up to 24 months |
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| 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. | 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. | Posted | Up to 24 months |
|
| |||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Up to 24 months |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Overall Survival (OS) | OS was defined as the time from the date of first dose to the date of death. | 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. | Posted | Up to 24 months |
|
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Percentage of Participants With MRD Negative Status as Determined by Next-Generation Sequencing (NGS) | 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. | Posted | Up to 24 months |
|
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Minimal Residual Disease (MRD) Negative Rate | 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. | Posted | Up to 12 months |
|
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Durable MRD Negative Rate | 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. | Posted | Up to 12 months |
|
|
From the first dose of study drug through 30 days after the last dose of study drug (up to 13 months)
The study was terminated after completion of Phase 1b Part 1, therefore, no participants were enrolled in Phase 1b-Part 2 and Phase 2 of this study. Hence, no safety data for Phase 1b-Part 2 and Phase 2 was collected, analyzed and reported in this AEs section.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG001 | 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. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG002 | 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. | 4 | 10 | 4 | 10 | 10 | 10 |
| EG003 | 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. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG004 | 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. | 4 | 8 | 3 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess limb | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| CD4 lymphocytes decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Cerumen impaction | Ear and labyrinth disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Ear disorder | Ear and labyrinth disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Epidural lipomatosis | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Osteolysis | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Painful respiration | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral sensorimotor neuropathy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Sialoadenitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Swelling | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
|
The study was terminated early due to business reasons.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 17, 2023 | Jul 30, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C000730454 | TAK-981 |
| C556306 | daratumumab |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 |
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
|
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
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