Study Stopped
Due to strategic reasons (no safety concerns).
A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma
iinnovate-2
A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma
2 other identifiers
interventional
15
4 countries
21
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 multiple-myeloma
Started Jan 2023
Shorter than P25 for phase_1 multiple-myeloma
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2022
CompletedFirst Posted
Study publicly available on registry
September 27, 2022
CompletedStudy Start
First participant enrolled
January 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 4, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 4, 2024
CompletedResults Posted
Study results publicly available
August 6, 2025
CompletedJanuary 29, 2026
January 1, 2026
1.4 years
September 23, 2022
April 25, 2025
January 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was defined by national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0: Grade 5 AE; Hematologic toxicity: Nonfebrile Grade 4 neutropenia lasting more than 7 consecutive days/Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 thrombocytopenia lasting more than 14 consecutive days, Grade 3 thrombocytopenia with clinically significant bleeding; any other Grade 4 with exceptions; Nonhematologic Grade 3 or higher toxicities unrelated to the underlying disease with exceptions.
Cycle 1 (Cycle length is 28 days)
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
Up to 16.7 months
Secondary Outcomes (15)
Progression Free Survival (PFS)
Up to 16.7 months
Overall Response Rate (ORR)
Up to 16.7 months
Duration of Response (DOR)
Up to 16.7 months
Groups 2 and 3: Overall Survival (OS)
Up to 16.7 months
Groups 2 and 3: Time to Progression (TTP)
Up to 16.7 months
- +10 more secondary outcomes
Study Arms (7)
Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Interventions
Modakafusp alfa intravenous infusion.
Lenalidomide capsules orally.
Bortezomib injection subcutaneously.
Carfilzomib intravenous infusion.
Daratumumab injection subcutaneously.
Pomalidomide capsules orally.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- +5 more criteria
You may not qualify if:
- 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.
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Scripps Health
San Diego, California, 92121, United States
The University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
Cancer Center At Greater Baltimore Medical Center
Baltimore, Maryland, 21153, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89119, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
New York University School of Medicine
New York, New York, 10016, United States
Weill Cornell Medicine/New York Presbyterian Hospital
New York, New York, 10021, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, 10065, United States
Novant Health Cancer Institute
Charlotte, North Carolina, 28204, United States
Novant Health Cancer Institute - Forsyth Medical Center
Winston-Salem, North Carolina, 27103, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
CHU UCL Namur site Godinne
Yvoir, Namur, 5530, Belgium
AZ Delta
Roeselare, Roeselare West-Vlaanderen, 8800, Belgium
Rambam Health Care Campus (RHCC) - Meyer Children's Hospital - Pediatric Diabetes & Obesity Clinic
Haifa, 31999, Israel
Clinica Universidad de Navarra-Sede Madrid
Madrid, 28027, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Clinica Universidad de Navarra, Dept of Oncology
Pamplona, 31008, Spain
Hospital Universitario La Fe de Valencia
Valencia, 46026, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Study was terminated early by sponsor for strategic reasons. No participants were enrolled in Group 2 Arm 4: modakafusp alfa + bortezomib \& Group 3 arms. Data for endpoints related to PFS, OS, DOR, TTP, TTNT, EFS, TTR, \& MRD were not collected as planned \& hence not reported.
Results Point of Contact
- Title
- Study Director
- Organization
- Teva U.S. Medical Information
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2022
First Posted
September 27, 2022
Study Start
January 12, 2023
Primary Completion
June 4, 2024
Study Completion
June 4, 2024
Last Updated
January 29, 2026
Results First Posted
August 6, 2025
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
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.