Multiple MyelomaPhase 1iinnovate-2NCT05556616
A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma
A Phase 1 study testing Modakafusp alfa, Lenalidomide and Bortezomib in people with Multiple Myeloma, run by Teva Branded Pharmaceutical Products R&D LLC at 21 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Modakafusp alfa, Lenalidomide and Bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 21 sitesin 4 countries
- Study dates
- 12 Jan 2023to 4 Jun 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Group 1 (MM maintenance: modakafusp alfa/lenalidomide) only must have:
- MM based on standard IMWG diagnostic criteria.
- 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.
- 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.
- 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).
- 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.
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- No prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
- 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.
- Groups 2 and 3 (RRMM doublets and RRMM triplets) must have:
- 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).
- 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.
- 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.
- 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.
- For anti-CD38 arms, forced expiratory volume in 1second (FEV1) >=50% predicted by pulmonary function testing.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening
- 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.
- 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).
Who cannot join
- 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.
- Received previous treatment with modakafusp alfa.
- 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.
- 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.
- Has evidence of central nervous system (CNS) involvement and/or meningeal involvement due to MM exhibited during screening.
- 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.
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- 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.
- Has a known history of seropositivity for HIV.
- 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.
- For bortezomib arms: participants received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization.
- 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.
- Has a QTcF (QT interval corrected with Fridericia correction method >480 millisecond (ms) (Grade >=2).
Trial locations and contacts
21 sites in 4 countries.
21 sites in 4 countries
United States14 sites
Cancer Center At Greater Baltimore Medical Center
Baltimore, Maryland, 21153
Gabrail Cancer Center Research
Canton, Ohio, 44718
Novant Health Cancer Institute
Charlotte, North Carolina, 28204
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
The University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89119
NYU Langone Hospital - Long Island
Mineola, New York, 11501
New York University School of Medicine
New York, New York, 10016
Weill Cornell Medicine/New York Presbyterian Hospital
New York, New York, 10021
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, 10065
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Scripps Health
San Diego, California, 92121
Novant Health Cancer Institute - Forsyth Medical Center
Winston-Salem, North Carolina, 27103
Spain4 sites
Clinica Universidad de Navarra-Sede Madrid
Madrid, 28027
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Clinica Universidad de Navarra, Dept of Oncology
Pamplona, 31008
Hospital Universitario La Fe de Valencia
Valencia, 46026
Belgium2 sites
AZ Delta
Roeselare, Roeselare West-Vlaanderen, 8800
CHU UCL Namur site Godinne
Yvoir, Namur, 5530
Israel1 site
Rambam Health Care Campus (RHCC) - Meyer Children's Hospital - Pediatric Diabetes & Obesity Clinic
Haifa, 31999
About this study
Official title: 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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Modakafusp alfa, Lenalidomide, Bortezomib, Carfilzomib, Daratumumab
- Keywords
- Drug Therapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modakafusp alfaDrug
Also called TAK-573
Modakafusp alfa intravenous infusion.
LenalidomideDrug
Lenalidomide capsules orally.
BortezomibDrug
Bortezomib injection subcutaneously.
CarfilzomibDrug
Carfilzomib intravenous infusion.
DaratumumabDrug
Daratumumab injection subcutaneously.
PomalidomideDrug
Pomalidomide capsules orally.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Lenalidomide |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Pomalidomide |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Carfilzomib |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Bortezomib |
| Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Bortezomib; Drug: Pomalidomide |
| Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Bortezomib; Drug: Pomalidomide |
| Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide | Experimental | 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. Receives: Drug: Modakafusp alfa; Drug: Daratumumab; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 16.7 months
Secondary outcomes (15)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 16.7 months
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb)
Measured: Up to 16.7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2022
- Study start12 Jan 2023
- Primary completion4 Jun 2024
- Study completion4 Jun 2024
Why it stopped: Due to strategic reasons (no safety concerns).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Teva Branded Pharmaceutical Products R&D LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05556616
- Sponsor's protocol ID
- TAK-573-1502
- Other IDs
- 2022-001418-20
- Acronym
- iinnovate-2
- Status last verified
- Jan 2026
- First submitted
- 23 Sep 2022
- Last updated
- 29 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05556616
- Acronym / sponsor ID
- iinnovate-2 / TAK-573-1502
- Conditions
- Multiple Myeloma
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to strategic reasons (no safety concerns).
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D LLCIndustry (pharma, biotech, devices)
- Study start
- 12 Jan 2023 (actual)
- Primary completion
- 4 Jun 2024 (actual)
- Study completion
- 4 Jun 2024 (actual)
- First posted
- 27 Sep 2022 (actual)
- Results
- Posted 6 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Experimental | Drug: Modakafusp alfa, Drug: LenalidomideParticipants 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. |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Experimental | Drug: Modakafusp alfa, Drug: PomalidomideParticipants 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. |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Experimental | Drug: Modakafusp alfa, Drug: CarfilzomibParticipants 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. |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 | Experimental | Drug: Modakafusp alfa, Drug: BortezomibParticipants 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. |
| Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib | Experimental | Drug: Modakafusp alfa, Drug: Bortezomib, Drug: PomalidomideParticipants 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. |
| Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib | Experimental | Drug: Modakafusp alfa, Drug: Bortezomib, Drug: PomalidomideParticipants 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. |
| Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide | Experimental | Drug: Modakafusp alfa, Drug: Daratumumab, Drug: PomalidomideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Group 1 (MM maintenance: modakafusp alfa/lenalidomide) only must have:
- Groups 2 and 3 (RRMM doublets and RRMM triplets) must have:
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening
- 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.
- 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).
Key exclusion criteria (12 listed)
- 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.
- Received previous treatment with modakafusp alfa.
- 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.
- 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.
- Has evidence of central nervous system (CNS) involvement and/or meningeal involvement due to MM exhibited during screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modakafusp alfaAlso: TAK-573Modakafusp alfa intravenous infusion. | Drug | Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg, Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib, Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2, Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg, Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg, Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib, Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide |
| LenalidomideLenalidomide capsules orally. | Drug | Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg |
| BortezomibBortezomib injection subcutaneously. | Drug | Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib, Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2, Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib |
| CarfilzomibCarfilzomib intravenous infusion. | Drug | Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg |
| DaratumumabDaratumumab injection subcutaneously. | Drug | Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide |
| PomalidomidePomalidomide capsules orally. | Drug | Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib, Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg, Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib, Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (Cycle length is 28 days)
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.
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 16.7 months
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.
15 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 16.7 months
Overall Response Rate (ORR)
Time frame: Up to 16.7 months
Duration of Response (DOR)
Time frame: Up to 16.7 months
Groups 2 and 3: Overall Survival (OS)
Time frame: Up to 16.7 months
Groups 2 and 3: Time to Progression (TTP)
Time frame: Up to 16.7 months
Groups 2 and 3: Time to Next Treatment (TTNT)
Time frame: Up to 16.7 months
Groups 2 and 3: Disease Control Rate (DCR)
Time frame: Up to 16.7 months
Groups 2 and 3: Event-free Survival (EFS)
Time frame: Up to 16.7 months
Groups 2 and 3: Time to Response (TTR)
Time frame: Up to 16.7 months
Group 1: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5
Time frame: 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
Time frame: Up to 2 years after CR confirmation
Duration of MRD Negativity Status at a Threshold of 10^-5 in Participants Achieving MRD Negativity
Time frame: Up to 2 years after treatment
Group 2 and 3: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5
Time frame: 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
Time frame: Up to 16.7 months
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb)
Time frame: Up to 16.7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Modakafusp alfa, Lenalidomide and Bortezomib in people with Multiple Myeloma, run by Teva Branded Pharmaceutical Products R&D LLC at 21 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Spain, Belgium, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (Cycle length is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.