A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma
NCT ID: NCT05556616
Last Updated: 2025-12-19
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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TERMINATED
PHASE1
15 participants
INTERVENTIONAL
2023-01-12
2024-06-04
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Lenalidomide
Lenalidomide capsules orally.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Pomalidomide
Pomalidomide capsules orally.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Carfilzomib
Carfilzomib intravenous infusion.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Bortezomib
Bortezomib injection subcutaneously.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Bortezomib
Bortezomib injection subcutaneously.
Pomalidomide
Pomalidomide capsules orally.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Bortezomib
Bortezomib injection subcutaneously.
Pomalidomide
Pomalidomide capsules orally.
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.
Modakafusp alfa
Modakafusp alfa intravenous infusion.
Daratumumab
Daratumumab injection subcutaneously.
Pomalidomide
Pomalidomide capsules orally.
Interventions
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Modakafusp alfa
Modakafusp alfa intravenous infusion.
Lenalidomide
Lenalidomide capsules orally.
Bortezomib
Bortezomib injection subcutaneously.
Carfilzomib
Carfilzomib intravenous infusion.
Daratumumab
Daratumumab injection subcutaneously.
Pomalidomide
Pomalidomide capsules orally.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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).
18 Years
ALL
No
Sponsors
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Takeda
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Takeda (Note: This product was divested to Teva Pharmaceuticals in 2025)
Locations
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University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Scripps Health
San Diego, California, United States
The University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States
Cancer Center At Greater Baltimore Medical Center
Baltimore, Maryland, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
NYU Langone Hospital - Long Island
Mineola, New York, United States
New York University School of Medicine
New York, New York, United States
Weill Cornell Medicine/New York Presbyterian Hospital
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, United States
Novant Health Cancer Institute
Charlotte, North Carolina, United States
Novant Health Cancer Institute - Forsyth Medical Center
Winston-Salem, North Carolina, United States
Gabrail Cancer Center Research
Canton, Ohio, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
CHU UCL Namur site Godinne
Yvoir, Namur, Belgium
AZ Delta
Roeselare, Roeselare West-Vlaanderen, Belgium
Rambam Health Care Campus (RHCC) - Meyer Children's Hospital - Pediatric Diabetes & Obesity Clinic
Haifa, , Israel
Clinica Universidad de Navarra-Sede Madrid
Madrid, , Spain
Hospital Universitario Virgen de la Victoria
Málaga, , Spain
Clinica Universidad de Navarra, Dept of Oncology
Pamplona, , Spain
Hospital Universitario La Fe de Valencia
Valencia, , Spain
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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To obtain more information about this study, click this link.
Other Identifiers
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2022-001418-20
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
TAK-573-1502
Identifier Type: -
Identifier Source: org_study_id