A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

NCT ID: NCT03215030

Last Updated: 2026-01-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

272 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-04

Study Completion Date

2024-11-07

Brief Summary

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The main aims of this 3-part study are as follows:

Part 1: To determine any side effects from modakafusp alfa single treatment and how often they occur. 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.

Part 2: To assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. Dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants.

Part 3: To find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa.

Participants will receive modakafusp alfa at one of two doses which will be given through a vein.

Detailed Description

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The drug being tested in this study, and which will be given through a vein, is called modakafusp alfa (TAK-573 ) as single agent or in combination with dexamethasone. The study will determine the safety, tolerability, and efficacy of modakafusp alfa as single agent and in combination with dexamethasone in participants with relapsed/refractory multiple myeloma (RRMM). The study consists of 3 Parts:

Part 1: Dose Escalation, Part 2: Dose Expansion, Part 3: Dose Extension

The study will enroll approximately 65 participants in Part 1, 35 in Part 2, and 236 in Part 3. Participants will be assigned to one of the following treatment groups in Parts 1 and 2 of the study. Participants will be randomly assigned in Part 3 of the study as given below:

* Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg
* Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD
* Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD
* Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD
* Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg
* Part 3 (Dose Extension): Modakafusp alfa 120 mg
* Part 3 (Dose Extension): Modakafusp alfa 240 mg

The Part 1 (Dose Escalation) portion of the study will follow a 3+3 dose escalation design to evaluate once-weekly up to 4 different schedules of administration of modakafusp alfa starting at 0.001 mg/kg for dose limiting toxicity (DLT) evaluation and to determine the maximum tolerated dose (MTD) or an optimal biological dose (OBD) for assessments in Part 2.

The Part 2 (Dose Expansion) will further assess the safety profile of modakafusp alfa and its efficacy at MTD or OBD.

For Part 3 (Dose Extension) participants will be randomized 1:1 to receive single-agent modakafusp alfa 120 mg or 240 mg Q4W.

Parts 1 and 2 will be conducted at multiple centers in the United States. Part 3 will be conducted worldwide. The maximum treatment duration in this study is up to 12 months (Parts 1 and 2) or until disease progression (Part 3) and overall time to participate in the study is approximately up to 90 months. Participants with clinical benefit may continue treatment after sponsor approval.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1 (Dose Escalation) Schedule A

Participants received Modakafusp alfa 0.001 up to 0.75 milligram per kilogram (mg/kg), infusion, intravenously (IV), once every week (Q1W) on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once every 2 weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once every 4 weeks (Q4W) on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 1 (Dose Escalation) Schedule B

Participants received Modakafusp alfa 0.20 up to 0.30 mg/kg, infusion, IV, Q2W on Days 1 and 15 of each 28-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 1 (Dose Escalation) Schedule C

Participants received Modakafusp alfa 0.40 up to 0.75 mg/kg, infusion, IV, once every 3 weeks (Q3W) on Day 1 of each 21-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 1 (Dose Escalation) Schedule D

Participants received Modakafusp alfa 1.5 up to 6.0 mg/kg, infusion, IV, Q4W on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 2 (Dose Expansion): Schedule C: Modakafusp Alfa

Participants received modakafusp alfa 0.400 mg/kg infusion, IV, Q3W on Day 1 of each 21-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 2 (Dose Expansion):ScheduleC:Modakafusp Alfa+Dexamethasone

Participants received modakafusp alfa 0.400 mg/kg infusion, IV, and dexamethasone 40 mg, orally, Q3W on Day 1 of each 21-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Dexamethasone

Intervention Type DRUG

Dexamethasone.

Part 2 (Dose Expansion): Schedule D: Modakafusp Alfa

Participants received modakafusp alfa 1.500 mg/kg infusion, IV, Q4W on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 2 (Dose Expansion): Schedule D: Modakafusp Alfa + Dexamethasone

Participants received modakafusp alfa 1.500 mg/kg infusion, IV, and dexamethasone 40 mg, orally, Q4W on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Dexamethasone

Intervention Type DRUG

Dexamethasone.

Part 3 (Dose Extension): Modakafusp Alfa 120 mg

Participants received modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Part 3 (Dose Extension): Modakafusp Alfa 240 mg

Participants received modakafusp alfa 240 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Japan Lead-in: Modakafusp Alfa 60 mg

Participants received modakafusp alfa 60 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Japan Lead-in: Modakafusp Alfa 120 mg

Participants received modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group Type EXPERIMENTAL

Modakafusp alfa

Intervention Type DRUG

Modakafusp alfa intravenous infusion.

Interventions

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Modakafusp alfa

Modakafusp alfa intravenous infusion.

Intervention Type DRUG

Dexamethasone

Dexamethasone.

Intervention Type DRUG

Other Intervention Names

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TAK-573 TEV-48573

Eligibility Criteria

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Inclusion Criteria

For Parts 1 and 2:

1\. Has MM defined by the IMWG criteria with evidence of disease progression and:

* In need of additional myeloma therapy as determined by the investigator.
* Has previously received at least 3 lines of myeloma therapy (for example, containing an Immunomodulatory imide drug \[IMiD\], a proteasome inhibitor \[PI\], an alkylating agent, and/or an anti-CD38 as single agents or in combination).
* Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD.

For Part 3:

1. Has MM defined by the IMWG criteria with evidence of disease progression and:

* In need of additional myeloma therapy as determined by the investigator.
* Has previously received at least 3 lines of myeloma therapy.
* Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide \[thalidomide excluded\]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. Participants who are primary refractory, meaning they never achieved at least a MR with any previous treatment line, are not eligible.
2. For participants in Part 2 and 3 only: Measurable disease is defined as :

1. Serum M-protein ≥500 mg/dL (≥5 g/L)
2. Urine M-protein ≥200 mg/24 hours.
3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. During Part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to \[≥ \] 10 percent \[%\]) and/or plasmacytoma (≥1 centimeter \[cm\] in diameter) detected by physical examination or imaging.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

Exclusion Criteria

For Parts 1 and 2:

1. Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).
2. Who have received autologous stem cell transplant (SCT) 60 days before first infusion of modakafusp alfa or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
3. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to (≤) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to ≤ Grade 2 or baseline.
4. Has clinical signs of central nervous system involvement of MM.

For Part 3:

* Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 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 \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded.
* In addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory MM, current central nervous system involvement of MM, myelodysplastic syndrome, myeloproliferative syndrome, or have had a second 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Teva Branded Pharmaceutical Products R&D LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Highlands Oncology Group

Springdale, Arkansas, United States

Site Status

Los Angeles Cancer Network - Glendale Adventist Medical Center

Glendale, California, United States

Site Status

University of California Irvine

Orange, California, United States

Site Status

Office of James R. Berenson MD

West Hollywood, California, United States

Site Status

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Northwestern Medicine - Northwestern Medical Group

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Investigative Clinical Research of Indiana, LLC

Noblesville, Indiana, United States

Site Status

June E. Nylen Cancer Center

Sioux City, Iowa, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Univeristy of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

USOR - Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, United States

Site Status

John Theurer Cancer Center

Hackensack, New Jersey, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Levine Cancer Center

Charlotte, North Carolina, United States

Site Status

Levine Cancer Institute - Concord

Concord, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Baptist Cancer Center - Memphis - Walnut Grove

Memphis, Tennessee, United States

Site Status

Lumi Research

Houston, Texas, United States

Site Status

British Columbia Cancer Agency Vancouver Centre

Vancouver, British Columbia, Canada

Site Status

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Site Status

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Peking University People's Hospital

Beijing, Beijing Municipality, China

Site Status

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

Wuhan Union Hospital

Wuhan, Hubei, China

Site Status

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status

The First Affiliated Hospital of Soochow University - Suzhou First People's Hospital

Suzhou, Jiangsu, China

Site Status

Shanghai Fourth People's Hospital

Shanghai, Shanghai Municipality, China

Site Status

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Site Status

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Site Status

Institut de cancerologie Strasbourg Europe

Strasbourg, Alsace, France

Site Status

Hopital Saint-Vincent de Paul - Lille

Lille, Hauts-de-France, France

Site Status

Centre Hospitalier Regional Universitaire de Lille

Lille, Hauts-de-France, France

Site Status

Centre Hospitalier Universitaire de Toulouse Hopital Purpan

Toulouse, Midi-pyrenees, France

Site Status

Centre Hospitalier Universitaire Nantes - Hotel Dieu

Nantes, Pays de la Loire Region, France

Site Status

Centre Hospitalier Universitaire de Poitiers

Poitiers, Poitou-charentes, France

Site Status

Centre Hospitalier d'Argenteuil - Centre Hospitalier Victor Dupouy

Argenteuil, , France

Site Status

Centre Hospitalier Universitaire Henri Mondor

Créteil, Île-de-France Region, France

Site Status

Hopital Saint-Antoine

Paris, Île-de-France Region, France

Site Status

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, France

Site Status

Universitatsklinik Tubingen

Tübingen, Baden-Wurttemberg, Germany

Site Status

Universitatsklinikum Leipzig

Leipzig, Saxony, Germany

Site Status

Evaggelismos General Hospital

Athens, Attica, Greece

Site Status

Alexandra General Hospital of Athens

Athens, Attica, Greece

Site Status

University Regional General Hospital of Patras

Patra, Peloponnese, Greece

Site Status

The Chaim Sheba Medical Center

Ramat Gan, Tel Aviv, Israel

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

AON SS Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Site Status

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, , Italy

Site Status

Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele

Catania, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Site Status

Ogaki Municipal Hospital

Gifu, Gifu, Japan

Site Status

University Hospital Kyoto Prefectural University of Medicine

Kyoto, Kyoto, Japan

Site Status

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, Japan

Site Status

Japanese Red Cross Medical Center

Tokyo, , Japan

Site Status

Oslo Universitetssykehus-Ulleval Hospital

Oslo, , Norway

Site Status

Ad-Vance Medical Research

Ponce, PR, Puerto Rico

Site Status

Hospital Espanol Auxilio Mutuo

San Juan, , Puerto Rico

Site Status

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

Tri-Service General Hospital

Taipei, Taipei CITY, Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Ankara Universitesi

Yenimahalle, Ankara, Turkey (Türkiye)

Site Status

Ondokuz Mayis Universitesi Tp Fakultesi

Samsun, , Turkey (Türkiye)

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, England, United Kingdom

Site Status

Royal Cornwall Hospital NHS Trust

Cornwell, England, United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom

Site Status

Genesis Care - Milton Keynes

Milton Keynes, England, United Kingdom

Site Status

Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, England, United Kingdom

Site Status

Genesis Care Windsor - Genesis Care UK Ltd.

Windsor, England, United Kingdom

Site Status

Countries

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United States Canada China France Germany Greece Israel Italy Japan Norway Puerto Rico South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Vogl DT, Atrash S, Holstein SA, Nadeem O, Benson D, Chaudry M, Biran N, Suryanarayan K, Li C, Liu Y, Collins S, Parot X, Kaufman JL. Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma. Blood. 2025 Feb 27;145(9):944-955. doi: 10.1182/blood.2024026124.

Reference Type DERIVED
PMID: 39630057 (View on PubMed)

Holstein SA, Atrash S, Mian H, Dimopoulos MA, Schjesvold F, Popat R, Shah N, Gatt ME, Gocke CB, Frenzel L, Touzeau C, Beksac M, Manier S, Magen H, Travis P, Nadeem O, Suryanarayan K, Li C, Li S, Nelson A, Cherepanov D, Parot X, Vogl DT. A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma. Blood. 2025 Aug 28;146(9):1051-1064. doi: 10.1182/blood.2024027873.

Reference Type DERIVED
PMID: 40279508 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TV48573-ONC-10128

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1195-8134

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-006038-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

jRCT2061220078

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-573-1501

Identifier Type: -

Identifier Source: org_study_id

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