Multiple MyelomaPhase 1/2iinnovate-3NCT05590377
A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing Modakafusp Alfa and Daratumumab in people with Multiple Myeloma, run by Teva Branded Pharmaceutical Products R&D LLC at 27 sites in 7 countries.
Trial summary
The main aim of this study is to determine safety and tolerability of modakafusp alfa given together with daratumumab to find out the best treatment dose. Another aim of this study is to learn more about the characteristics of 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 and Daratumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 27 sitesin 7 countries
- Study dates
- 23 Jan 2023to 22 May 2024
- Phase
- Phase 1/2
- 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
- Documented multiple myeloma (MM) diagnosis per IMWG criteria.
- Measurable disease, defined as at least 1 of the following:
- Serum M protein ≥0.5 grams per deciliter [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 with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
- For participants in the Phase 1 Dose Escalation only:
Show all 14Show fewer
- Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy.
- For participants in Phase 2a Dose Finding only:
- Received 1 to 3 prior line(s) of antimyeloma therapy.
- Must be refractory to prior lenalidomide treatment.
- Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment.
- Documented progressive disease on or after the last regimen.
- Participants must have PR or better to at least 1 line of prior therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.
Who cannot join
- Prior exposure to modakafusp alfa.
- Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
- Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade ≤1 or baseline, except for alopecia.
- Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
- Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
- Participant has congestive heart failure (New York Heart Association Grade ≥II), cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension.
- Participant has QT interval corrected by the Fridericia method >480 milliseconds [msec] (Grade ≥2).
- Participant has a chronic condition that will require the chronic use of systemic corticosteroids >10 milligrams per day (mg/d) of prednisone or equivalent on top of any required corticosteroids for multiple myeloma (MM).
Trial locations and contacts
27 sites in 7 countries.
27 sites in 7 countries
United States13 sites
New York Cancer and Blood Specialists
Bay Shore, New York, 11706
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, 02111
University of Cincinnati - Vontz Center for Molecular Studies
Cincinnati, Ohio, 45267
Summit Medical Group PA
Florham Park, New Jersey, 07932
Fort Wayne Medical Oncology and Hematology, Inc
Fort Wayne, Indiana, 46060
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Cedars-Sinai Medical Center
Los Angeles, California, 77598
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
University of Nebraska Medical Center
Omaha, Nebraska, 68198
HCA Midwest Health (Midwest Ventures Group HCA MidAmerica Division)
Overland Park, Kansas, 66211
Washington University School of Medicine
St Louis, Missouri, 63130
Stony Brook University Hospital
Stony Brook, New York, 11794
Tranquil Clinical Research
Webster, Texas, 78041
China4 sites
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
Zhejiang University School of Medicine - The First Affiliated Hospital (Zhejiang Provincial First Hospital)
Hangzhou, Zhejiang, 310003
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin Municipality, 300020
Wuhan Union Hospital
Wuhan, Hubei, 430022
South Korea3 sites
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, Seoul St. Marys Hospital
Seoul, 06591
Australia2 sites
Concord Repatriation General Hospital
Concord, New South Wales, 2139
The Alfred Hospital
Melbourne, Victoria, 3004
France2 sites
CHRU Lille
Lille, Hauts-de-France, 59037
Institut Paoli-Calmettes
Marseille, Provence-Alpes-Côte d'Azur Region, 13273
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Fundacion Instituto de Estudios Ciencias de la Salud de Castilla y Leon-Investigacion Biomedica de Salamanca (IBSAL)
Salamanca, 37007
Canada1 site
Centre Hospitalier Universitaire De Sherbrooke (CHUS) - Centre de Recherche Clinique Etienne-Le Bel (CRCELB) Hopital Fleurimont
Sherbrooke, Quebec, J1H 5N4
About this study
Official title: A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma
The main aim of this study is to determine safety and tolerability of modakafusp alfa given together with daratumumab to find out the best treatment dose. Another aim of this study is to learn more about the characteristics of modakafusp alfa.
Read the detailed description
The drug being tested in this study is called modakafusp alfa (TAK-573). Modakafusp alfa is being tested to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy in combination with daratumumab in participants with relapsed or refractory multiple myeloma (RRMM). The study will consist of 2 phases: Phase 1 Dose Escalation and a Phase 2a Dose Finding.
The study will enroll approximately 58 patients. Approximately 18 participants will be enrolled in the Phase 1 Dose Escalation/De-escalation and two dose levels of modakafusp alfa in combination with daratumumab SC will be selected to be further explored in the randomized Phase 2a Dose Finding part of the study wherein, approximately 40 participants will be randomly assigned by chance (like flipping a coin) to one of the two treatment groups:
- Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab
- Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 60 months. Participants who discontinue study drug treatment for reasons other than progressive disease will continue progression-free survival (PFS) follow-up every 4 weeks from the end of treatment (EOT) visit until the occurrence of progressive disease, death, the start of subsequent systemic antineoplastic therapy, study termination, whichever occurs first.
- Conditions
- Multiple Myeloma
- Being tested
- Modakafusp Alfa, 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
DaratumumabDrug
Daratumumab SC injection
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Experimental | Modakafusp alfa 80 mg, infusion, intravenously (IV), once every 4 weeks (Q4W) with daratumumab 1800 mg, subcutaneously (SC), once weekly (QW) in Cycles 1 and 2, twice weekly (Q2W) in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. Receives: Drug: Modakafusp Alfa; Drug: Daratumumab |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Experimental | Modakafusp alfa 120 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. Receives: Drug: Modakafusp Alfa; Drug: Daratumumab |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Experimental | Modakafusp alfa 240 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. Receives: Drug: Modakafusp Alfa; Drug: Daratumumab |
| Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab | Experimental | Modakafusp alfa at dose level 1 (DL1) [selected from Phase 1 Dose Escalation] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. Receives: Drug: Modakafusp Alfa; Drug: Daratumumab |
| Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab | Experimental | Modakafusp alfa at dose level 2 (DL2) [selected from Phase 1 Dose Escalation] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. Receives: Drug: Modakafusp Alfa; Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)
DLT was defined as any of the treatment-emergent adverse events (TEAEs) that occurred during Cycle 1 and were considered by the investigator to be at least possibly related to modakafusp alfa. Toxicity was evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0.
Measured: Phase 1: Cycle 1 (cycle length=28 days)
Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Severity grades for TEAEs were evaluated as per the NCI CTCAE Version 5.0.
Measured: Phase 1: Up to 15.9 months
Phase 2a: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a confirmed partial response (PR) or better during the study in the safety population. ORR will be assessed by the investigator per International Myeloma Working Group (IMWG) criteria.
Measured: Phase 2a: Up to 15.9 months
Secondary outcomes (30)
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Apparent Serum Terminal Disposition Rate Constant for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Total Clearance After Intravenous Administration for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Volume of Distribution at Steady State After Intravenous (IV) Administration for Modakafusp Alfa
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Daratumumab
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Ctrough: Single-Dose and Multiple-dose Observed Concentration at the End of a Dosing Interval for Daratumumab
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Daratumumab
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Daratumumab
Measured: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a confirmed PR or better during the study in the safety population. ORR will be assessed by the investigator per IMWG criteria.
Measured: Phase 1: Up to 15.9 months
Phase 1 and Phase 2a: Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. DOR will be calculated for confirmed responders only (PR or better). DOR will be assessed by the investigator as per IMWG criteria.
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose administration of any study drug to the first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. PFS will be assessed by the investigator as per IMWG criteria.
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Overall Survival (OS)
OS is defined as the time from the date of the first dose administration of any study drug to the documentation of death due to any cause. OS will be assessed by the investigator as per IMWG criteria.
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA)
After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons and hence no participants were enrolled for Phase 2a.
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Titer of Anti-drug Antibodies
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Rate of Measurable [Minimal] Residual Disease Negative (MRD[-]) Complete Response (CR)
MRD[-] CR rate is defined as the percentage of participants who achieve confirmed CR assessed by the investigator and MRD[-] status using a threshold of 10^-5. The analysis will be based on the response-evaluable population. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero.
Measured: Up to 15.9 months
Phase 1 and Phase 2a: Duration of Measurable [Minimal] Residual Disease (MRD) Negativity
Duration of MRD negativity for participants achieving MRD negativity is defined as the time from the date of first documentation of MRD negativity to the first documentation of MRD positivity or confirmed progressive disease, whichever occurs first. It will be calculated for participants achieving MRD negativity only. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero.
Measured: Up to 15.9 months
Phase 2a: Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants who had a confirmed response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response based on investigators' disease assessment per IMWG criteria.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Duration of Clinical Benefit (DCB)
DCB is defined as the time from the date of first documentation of a minimal response or better to the date of first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. DCB will be calculated for only participants who achieved a minimal response or better. DCB will be assessed by the investigator as per IMWG criteria.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed response of sCR, CR, VGPR, PR, minimal response, or stable disease (SD) based on investigators' disease assessment per IMWG criteria.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Duration of Disease Control
Duration of disease control is defined as the time from date of first documentation of SD or better to the date of first documentation of confirmed progressive disease or death due to any cause. Duration of disease control will be calculated for only patients who achieved SD or better. It will be assessed by the investigator per IMWG criteria.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Time to Progression (TTP)
TTP is defined as the time from the date of randomization to the first documentation of confirmed progressive disease as defined by IMWG criteria, assessed by the investigator. Participants without documentation of confirmed progression will be censored at the date of last adequate disease assessment. The analysis will be based on the intent-to-treat (ITT) population.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Time to Response (TTR)
TTR is defined as time from the date of first dose administration of any study drug to the date of the first documentation of a confirmed PR or better. TTR will be calculated for responders only. TTR will be assessed by the investigator per IMWG criteria.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Time to Next Treatment (TTNT)
TTNT is defined as the time from the date of first dose administration of any study drug to the date of the first dose initiation of the next line of anticancer therapy for any reason or death from any cause, whichever comes first. Participants who have not started the next-line therapy will be censored at the date last known to be alive before subsequent anticancer therapy.
Measured: Phase 2a: Up to 15.9 months
Phase 2a: Number of Participants Reporting One or More TEAEs and Per Severity
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Severity grades for TEAEs will be evaluated as per the NCI CTCAE Version 5.0.
Measured: Phase 2a: Up to 15.9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2022
- Study start23 Jan 2023
- Primary completion22 May 2024
- Study completion22 May 2024
Why it stopped: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a and the study was terminated early.
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 1/2
- 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
- NCT05590377
- Sponsor's protocol ID
- TAK-573-2001
- Other IDs
- 2022-002169-14
- Acronym
- iinnovate-3
- Status last verified
- Jan 2026
- First submitted
- 19 Oct 2022
- Last updated
- 30 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 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT05590377
- Acronym / sponsor ID
- iinnovate-3 / TAK-573-2001
- Conditions
- Multiple Myeloma
- Keywords
- Drug Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a and the study was terminated early.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 22 May 2024 (actual)
- Study completion
- 22 May 2024 (actual)
- First posted
- 21 Oct 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 aim of this study is to determine safety and tolerability of modakafusp alfa given together with daratumumab to find out the best treatment dose. Another aim of this study is to learn more about the characteristics of modakafusp alfa.
Detailed description
The drug being tested in this study is called modakafusp alfa (TAK-573). Modakafusp alfa is being tested to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy in combination with daratumumab in participants with relapsed or refractory multiple myeloma (RRMM). The study will consist of 2 phases: Phase 1 Dose Escalation and a Phase 2a Dose Finding.
The study will enroll approximately 58 patients. Approximately 18 participants will be enrolled in the Phase 1 Dose Escalation/De-escalation and two dose levels of modakafusp alfa in combination with daratumumab SC will be selected to be further explored in the randomized Phase 2a Dose Finding part of the study wherein, approximately 40 participants will be randomly assigned by chance (like flipping a coin) to one of the two treatment groups:
- Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab
- Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 60 months. Participants who discontinue study drug treatment for reasons other than progressive disease will continue progression-free survival (PFS) follow-up every 4 weeks from the end of treatment (EOT) visit until the occurrence of progressive disease, death, the start of subsequent systemic antineoplastic therapy, study termination, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Experimental | Drug: Modakafusp Alfa, Drug: DaratumumabModakafusp alfa 80 mg, infusion, intravenously (IV), once every 4 weeks (Q4W) with daratumumab 1800 mg, subcutaneously (SC), once weekly (QW) in Cycles 1 and 2, twice weekly (Q2W) in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Experimental | Drug: Modakafusp Alfa, Drug: DaratumumabModakafusp alfa 120 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Experimental | Drug: Modakafusp Alfa, Drug: DaratumumabModakafusp alfa 240 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. |
| Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab | Experimental | Drug: Modakafusp Alfa, Drug: DaratumumabModakafusp alfa at dose level 1 (DL1) [selected from Phase 1 Dose Escalation] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. |
| Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab | Experimental | Drug: Modakafusp Alfa, Drug: DaratumumabModakafusp alfa at dose level 2 (DL2) [selected from Phase 1 Dose Escalation] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Documented multiple myeloma (MM) diagnosis per IMWG criteria.
- Measurable disease, defined as at least 1 of the following:
- For participants in the Phase 1 Dose Escalation only:
- Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy.
- For participants in Phase 2a Dose Finding only:
Key exclusion criteria (8 listed)
- Prior exposure to modakafusp alfa.
- Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
- Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade ≤1 or baseline, except for alopecia.
- Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
- Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
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 | Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab, Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab, Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab, Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab, Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab |
| DaratumumabDaratumumab SC injection | Drug | Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab, Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab, Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab, Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab, Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab |
Primary outcome
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)
Time frame: Phase 1: Cycle 1 (cycle length=28 days)
DLT was defined as any of the treatment-emergent adverse events (TEAEs) that occurred during Cycle 1 and were considered by the investigator to be at least possibly related to modakafusp alfa. Toxicity was evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0.
Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity
Time frame: Phase 1: Up to 15.9 months
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Severity grades for TEAEs were evaluated as per the NCI CTCAE Version 5.0.
Phase 2a: Overall Response Rate (ORR)
Time frame: Phase 2a: Up to 15.9 months
ORR is defined as the percentage of participants who achieve a confirmed partial response (PR) or better during the study in the safety population. ORR will be assessed by the investigator per International Myeloma Working Group (IMWG) criteria.
30 secondary outcomes
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Apparent Serum Terminal Disposition Rate Constant for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Total Clearance After Intravenous Administration for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Volume of Distribution at Steady State After Intravenous (IV) Administration for Modakafusp Alfa
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Daratumumab
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Ctrough: Single-Dose and Multiple-dose Observed Concentration at the End of a Dosing Interval for Daratumumab
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Daratumumab
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Daratumumab
Time frame: Phase 1: Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Phase 1: Overall Response Rate (ORR)
Time frame: Phase 1: Up to 15.9 months
Phase 1 and Phase 2a: Duration of Response (DOR)
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Progression Free Survival (PFS)
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Overall Survival (OS)
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA)
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Titer of Anti-drug Antibodies
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Rate of Measurable [Minimal] Residual Disease Negative (MRD[-]) Complete Response (CR)
Time frame: Up to 15.9 months
Phase 1 and Phase 2a: Duration of Measurable [Minimal] Residual Disease (MRD) Negativity
Time frame: Up to 15.9 months
Phase 2a: Clinical Benefit Rate (CBR)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Duration of Clinical Benefit (DCB)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Disease Control Rate (DCR)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Duration of Disease Control
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Time to Progression (TTP)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Time to Response (TTR)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Time to Next Treatment (TTNT)
Time frame: Phase 2a: Up to 15.9 months
Phase 2a: Number of Participants Reporting One or More TEAEs and Per Severity
Time frame: Phase 2a: Up to 15.9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 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.
27 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Modakafusp Alfa and Daratumumab in people with Multiple Myeloma, run by Teva Branded Pharmaceutical Products R&D LLC at 27 sites in 7 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 14 inclusion and 8 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 30 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 27 sites in United States, China, South Korea, Australia, France and 2 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT) (time frame: Phase 1: Cycle 1 (cycle length=28 days)). The study lists 3 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 30 Jan 2026.