A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (iinnovate-2)

A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma

The main aims of this study are to test for any side effects from modakafusp alfa in combination therapy and to determine the recommended dose of combination therapy with modakafusp alfa. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found. Participants will be given modakafusp alfa through a vein.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Modakafusp alfa; Drug: Lenalidomide; Drug: Pomalidomide; Drug: Bortezomib; Drug: Carfilzomib; Drug: Daratumumab

Detailed Description

The drug being tested in this study is called modakafusp alfa (TAK-573). The study will evaluate the safety, tolerability and determine the recommended dose of modakafusp alfa in combination with lenalidomide in participants with multiple myeloma (MM), or in combination with pomalidomide, bortezomib, carfilzomib, or daratumumab in participants with relapsed/refractory multiple myeloma (RRMM).

The study consists of 3 Groups: Group 1: MM Maintenance Therapy, Group 2: RRMM Doublets, Group 3: RRMM Triplets.

The study will enroll approximately 18 participants in Group 1, 66 in Group 2, and 36 in Group 3. Participants will be assigned to one of the following treatment groups as given below:

• Group 1 (MM Maintenance) Arm 1: Modakafusp alfa + Lenalidomide
• Group 2 (RRMM Doublets) Arm 2: Modakafusp alfa + Pomalidomide
• Group 2 (RRMM Doublets) Arm 3: Modakafusp alfa + Bortezomib
• Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Carfilzomib
• Group 3 RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib
• Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide

Group 2 Arm 4 is closed for enrollment.

The study will be conducted worldwide. The maximum treatment duration in this study for Group 1 is until disease progression or unacceptable toxicity, or up to 2 years for minimal/measurable residual disease (MRD) negative [-] participants, whichever occurs first. The maximum treatment duration in this study for Group 2 and Group 3 is until disease progression, unacceptable toxicity or until any other discontinuation criterion is met, whichever occurs first. Overall time to participate in the study is approximately up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • CHU UCL Namur Site Godinne
  • Roeselare West-Vlaanderen
    • Roeselare, Roeselare West-Vlaanderen, Belgium, 8800
      • AZ Delta
• Israel
  • Haifa, Israel, 31999
    • Rambam Health Care Campus (RHCC) - Meyer Children's Hospital - Pediatric Diabetes & Obesity Clinic
• Spain
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra-Sede Madrid
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra, Dept of Oncology
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe de Valencia
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92121
      • Scripps Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospitals & Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21153
      • Cancer Center At Greater Baltimore Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - Main Campus
    • New York, New York, United States, 10021
      • Weill Cornell Medicine/New York Presbyterian Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Cancer Institute - Forsyth Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Group 1 (MM maintenance: modakafusp alfa/lenalidomide) only must have:

   1. MM based on standard IMWG diagnostic criteria.
   2. Undergone autologous stem cell transplantation (ASCT) for the treatment of MM within 12 months of the start of induction therapy and completed ASCT within 180 days before enrollment- (regardless of the lines of treatment).Consolidation cycles are allowed. Tandem transplant is allowed.
   3. Not started lenalidomide maintenance before enrollment. Time to initiation of maintenance therapy: participants may start maintenance therapy as early as 60 days after transplantation and up to 180 days after transplantation or consolidation.
   4. MRD positive ( after ASCT (MRD assessed at a threshold of 10^-5 by local standard-of-care (SOC) methods or central assessment, if a prior local MRD assessment had not been performed).
   5. No prior progression after initial therapy (at any time before starting maintenance). Participants whose induction therapy was changed due to suboptimal response or toxicity will be eligible if they do not meet criteria for progression. In addition, no more than 2 regimens will be allowed before ASCT, excluding dexamethasone alone.
   6. No prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
   7. Recovered to Grade less than or equal to (<=) 1 ASCT-related toxicities from the reversible effects of ASCT (except for alopecia and amenorrhea). MM based on standard IMWG diagnostic criteria.

2. Groups 2 and 3 (RRMM doublets and RRMM triplets) must have:

   1. Measurable disease, defined as at least 1 of the following:

      • Serum M-protein >=0.5 g/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
      • Urine M-protein >=200 mg/24 hours on urine protein electrophoresis (UPEP).
      • Serum free light chain (FLC) assay result with an involved FLC level >=10 mg/dL (>=100 mg/L), provided the serum FLC ratio is abnormal (per IMWG criteria).
   2. A confirmed diagnosis of MM according to International Myeloma Working Group (IMWG) criteria with documented disease progression in need of additional therapy as determined by the investigator.
   3. For Group 2 RRMM doublet arms only: Participants who have received at least 3 prior lines of antimyeloma therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory drug (IMiD) and 1 anti-CD38 monoclonal antibody (mAb) drug, or who are triple refractory to a PI, and IMiD, and an anti-CD38 mAb drug regardless of the number of prior line(s) of therapy.

   d. For Group 3 RRMM triplet arms only: Participants who have received 1 to 3 prior lines of antimyeloma therapy including at least 1 PI and, 1 IMiD, and who are not refractory to the combination partners.

   e) For anti-CD38 arms, forced expiratory volume in 1second (FEV1) >=50% predicted by pulmonary function testing.

3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening
4. Has adequate organ function at screening as determined by the laboratory values required for enrollment: Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (or >=1*10^9/L); Platelets >=75,000/mm^3 (>=75*10^9/L); Hemoglobin >=8.0 g/dL; estimated creatinine clearance >=30 mL/min (Cockcroft-Gault formula); Total serum bilirubin <=2.0*Upper limit of normal (ULN); an exception for participants with Gilbert's syndrome may be granted after discussion with the sponsor; Liver transaminases (alanine aminotransferase [ALT])/aspartate aminotransferase [AST]) <=3.0*ULN.
5. Has recovered from adverse reactions to prior myeloma treatment or procedures (example, chemotherapy, immunotherapy, radiation therapy) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade <=1 or baseline treatment or have the toxicity established as sequela, except for sensory or motor neuropathy, which should have recovered to Grade <=2 or baseline; ; (Grade 1 for the bortezomib arm).

Exclusion criteria:

1. Currently participating in another MM interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) throughout the duration of this study.
2. Received previous treatment with modakafusp alfa.
3. Has a diagnosis of primary amyloidosis, Waldenström disease, monoclonal gammopathy of undetermined significance or smoldering MM per IMWG criteria or standard diagnostic criteria, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), lymphoplasmacytic lymphoma.
4. Has been diagnosed with another malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy and that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.
5. Has evidence of central nervous system (CNS) involvement and/or meningeal involvement due to MM exhibited during screening.
6. Has a known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the modakafusp alfa formulation or to the study combination agents, the study medications, their analogs, or excipients in the various formulations of any agent per the prescribing information.
7. Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and, a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
8. Has a known history of seropositivity for HIV.
9. Has a known history of seropositivity for hepatitis C (anti-hepatitis C virus [HCV] antibody positive or anti-hepatitis C virus-RNA quantitation positive). Exception: Participants with a sustained virologic response with undetectable HCV RNA level at least 12 weeks after completion of antiviral therapy.
10. For bortezomib arms: participants received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization.
11. The participant has a chronic condition requiring the use of systemic corticosteroids >10 mg/dL of prednisone or equivalent, in addition to any required corticosteroids for the treatment of MM.
12. Has a QTcF (QT interval corrected with Fridericia correction method >480 millisecond (ms) (Grade >=2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg; Participants received 80 milligrams (mg) modakafusp alfa, infusion intravenously (IV), once on Day 1, once every 4 weeks (Q4W), in combination with 10 mg lenalidomide capsules orally once daily continuously on Days 1 to 28, in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or to a maximum of 2 years for measurable/minimal residual disease-negative (MRD [-]) participants, whichever occurred first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Lenalidomide; Lenalidomide capsules orally.
Experimental: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg; Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 2 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Pomalidomide; Pomalidomide capsules orally.
Experimental: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg; Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 4 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Carfilzomib; Carfilzomib intravenous infusion.
Experimental: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2; Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 20/70 milligrams per meter square (mg/m^2) carfilzomib IV, on Day 1, 8 and 15 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Bortezomib; Bortezomib injection subcutaneously.
Experimental: Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib; Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with bortezomib injection subcutaneously on Days 8, 15, and 22 for the first 8 cycles and subsequently on Days 8 and 22 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Pomalidomide; Pomalidomide capsules orally.; Drug: Bortezomib; Bortezomib injection subcutaneously.
Experimental: Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib; Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle along with bortezomib injection subcutaneously on Days 8, 15 and 22 for the first 8 cycles and subsequently on Days 8 and 22 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Pomalidomide; Pomalidomide capsules orally.; Drug: Bortezomib; Bortezomib injection subcutaneously.
Experimental: Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide; Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with daratumumab injection subcutaneously on Days 1, 8, 15 and 22 of Cycles 1 and 2, further followed by on Days 1 and 15 of Cycles 3 to 6, thereafter on Day 1 on a 28-day (4-week) treatment cycle along with pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa; Modakafusp alfa intravenous infusion.; Other Names: TAK-573; Drug: Pomalidomide; Pomalidomide capsules orally.; Drug: Daratumumab; Daratumumab injection subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs)	DLT was defined by national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0: Grade 5 AE; Hematologic toxicity: Nonfebrile Grade 4 neutropenia lasting more than 7 consecutive days/Grade greater than or equal to (>=) 3 febrile neutropenia; Grade 4 thrombocytopenia lasting more than 14 consecutive days, Grade 3 thrombocytopenia with clinically significant bleeding; any other Grade 4 with exceptions; Nonhematologic Grade 3 or higher toxicities unrelated to the underlying disease with exceptions.	Cycle 1 (Cycle length is 28 days)
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.	Up to 16.7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from the date on which the first dose of study drug is administered to the date of first documentation of confirmed progression of disease (PD) or death due to any cause, whichever occurs first. PD was determined by International Myeloma Working Group (IMWG) criteria. PD: increase of ≥25 percent (%) from lowest response value in any one or more of the following: serum M-component increase ≥0.5 gram per deciliter (g/dL) or urine M-component increase ≥200 milligram (mg)/24-hour; difference between involved and uninvolved free light chains (FLC) levels increase must be greater than (>) 10 milligram per deciliter (mg/dL); bone marrow plasma cell ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 16.7 months
Overall Response Rate (ORR)	ORR: percentage of participants achieving confirmed partial response rate(PR)or better(stringent complete response[sCR]+complete response[CR]+very good partial response[VGPR]+PR)during study as defined by IMWG uniform response criteria and as determined by investigator.PR:>=50%reduction of serum M-protein and>=90% reduction in urine M-protein or less than(<)200mg/24 hour, or>=50%decrease in uninvolved FLC or >=50% reduction in plasma cells. At baseline,a >=50% decrease in size of soft tissue plasmacytomas was required. Percentages were rounded off to nearest single decimal place. Due to early termination of study no participants were enrolled in Group 2 Arm 4: modakafusp alfa+bortezomib and Group 3 arms, thus they are not presented here. Also, no participants in Group 1 fulfilled criteria for Response-Evaluable Analysis Set, hence are not presented here. Given limited number of participants and low confidence interval as a consequence, those response rate provides limited information.	Up to 16.7 months
Duration of Response (DOR)	DOR was defined as the time from the date of first documentation of confirmed PR or better (sCR+ CR+ VGPR+ PR) to the date of first documentation of PD or death due to any cause. PR: >=50% reduction of serum M-protein and >=90% reduction in urine M-protein or <200 mg/24 hour, or >=50% decrease in uninvolved FLC or >=50% reduction in plasma cells. At baseline, a >=50% decrease in size of soft tissue plasmacytomas is required. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 16.7 months
Groups 2 and 3: Overall Survival (OS)	OS was defined as the time from the first dose of administration to the date of death, due to any cause. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.	Up to 16.7 months
Groups 2 and 3: Time to Progression (TTP)	TTP was defined as the time from the date of the first dose until the earliest date of confirmed PD per IMWG, or death due to PD. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 16.7 months
Groups 2 and 3: Time to Next Treatment (TTNT)	TTNT was defined as the time from the date of first dose administration to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.	Up to 16.7 months
Groups 2 and 3: Disease Control Rate (DCR)	DCR was defined as the percentage of participants who achieved a stable disease (SD) or better during the study based on the investigator's disease assessment as defined by IMWG uniform response criteria. SD was defined as no known evidence of progressive disease or new bone lesions. Percentages were rounded off to the nearest single decimal place.	Up to 16.7 months
Groups 2 and 3: Event-free Survival (EFS)	EFS was defined as the time from the date on which the first dose of study drug is administered to the date of the first documentation of an event that may include confirmed PD, discontinuation of a treatment for an AE (related or not related), or death due to any cause, whichever occurs first. PD was determined by IMWG criteria. PD: increase of >=25 % from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be > 10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 16.7 months
Groups 2 and 3: Time to Response (TTR)	TTR was defined as the time from the date of the first dose administration to the date of the first documentation of objective confirmed response as defined by IMWG criteria.	Up to 16.7 months
Group 1: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5	Rate of MRD negativity at a sensitivity of 10^-5 was defined as the percentage of participants who achieved MRD negative status in the MRD-evaluable analysis set.	At 6 months, 1 year, and 2 years after the start of treatment
Groups 2 and 3: Percentage of Participants With MRD Negativity CR Status at a Threshold of 10^-5 in Participants Achieving CR Assessed by the Investigator	Rate of MRD negativity CR status a sensitivity of 10^-5 was defined as the percentage of participants who have achieved MRD negative CR status in participants achieving CR. CR is defined as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required.	Up to 2 years after CR confirmation
Duration of MRD Negativity Status at a Threshold of 10^-5 in Participants Achieving MRD Negativity	Duration of MRD negativity (10^-5) was defined as the time from the date of first documentation of MRD[-] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 2 years after treatment
Group 2 and 3: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5	Rate of MRD negativity at a sensitivity of 10^-5 was defined as the percentage of participants who have achieved MRD negative status.	Up to 16.7 months
Groups 2 and 3: Duration of MRD Negativity Status at a Sensitivity Threshold of 10^-5 in Participants Achieving MRD Negativity	Duration of MRD negativity (10^-5) was defined as the time from the date of first documentation of MRD[-] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to 16.7 months
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb)		Up to 16.7 months

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D LLC
• Investigators: Study Director: Medical Director, Takeda (Note: This product was divested to Teva Pharmaceuticals in 2025)

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Actual): June 4, 2024
• Study Completion (Actual): June 4, 2024

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Inorganic Chemicals; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; carfilzomib; pomalidomide; daratumumab
• Other Study ID Numbers: TAK-573-1502; 2022-001418-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be assessed for scientific merit, product approval status, and conflicts of interest. If the request is approved, patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please visit USMedInfo@tevapharm.com to make your request.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No