A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments (MAGNETISMM-5)

AN OPEN-LABEL, 3-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) MONOTHERAPY AND ELRANATAMAB + DARATUMUMAB VERSUS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 1 PRIOR LINE OF THERAPY INCLUDING LENALIDOMIDE AND A PROTEASOME INHIBITOR

The purpose of this clinical trial is to (1) learn whether the BCMA-CD3 bispecific antibody elranatamab can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone, and (2) learn about the safety and activity of elranatamab in combination with the anti-CD38 monoclonal antibody daratumumab. People with multiple myeloma who have received previous treatment including lenalidomide will be enrolled in the study.

Part 1 of the study will assess the safety and activity of different doses of elranatamab in combination with daratumumab.

People participating in Part 2 of the study will be randomly assigned to receive either elranatamab alone, elranatamab plus daratumumab, or daratumumab, pomalidomide, and dexamethasone. Part 2 will evaluate the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab.

Part 3 will assess the effect of increased measures to protect against infection in people treated with either elranatamab alone or together with daratumumab.

All people participating in the study will receive study treatment until their disease progresses, they experience unacceptable side effects, or they choose to no longer participate in the study.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Elranatamab; Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 944
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Argentina
  • Buenos Aires
    • Presidente Derqui, Buenos Aires, Argentina, B1629AHJ
      • Active, not recruiting
      • Hospital Universitario Austral
• Australia
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
    • Clayfield, Queensland, Australia, 4011
      • Recruiting
      • QScan Radiology Clinics
    • Greenslopes, Queensland, Australia, 4120
      • Active, not recruiting
      • Gallipoli Medical Research Foundation
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Recruiting
      • Slade Pharmacy
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Active, not recruiting
      • Linear Clinical Research
• Brazil
  • Rio de Janeiro, Brazil, 22793-080
    • Active, not recruiting
    • Instituto de Educação, Pesquisa e Gestão em Saúde
  • São Paulo, Brazil, 04024-002
    • Active, not recruiting
    • HU UNIFESP / SPDM - Hospital São Paulo
  • São Paulo, Brazil, 04537-080
    • Active, not recruiting
    • Clinica Medica Sao Germano S/S LTDA
  • São Paulo, Brazil, 04543-000
    • Active, not recruiting
    • Instituto D'Or de Pesquisa e Ensino (IDOR)
  • São Paulo, Brazil, 04544-000
    • Active, not recruiting
    • Instituto D'Or de Pesquisa e Ensino (IDOR)
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Active, not recruiting
      • Instituto D'Or de Pesquisa e Ensino (IDOR) - Filial Salvador
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Active, not recruiting
      • Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
    • Porto Alegre, Rio Grande do Sul, Brazil, 90880-480
      • Active, not recruiting
      • Hospital Mae de Deus
  • São Paulo
    • SP, São Paulo, Brazil, 04537-080
      • Active, not recruiting
      • Clínica Médica São Germano LTDA
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T2M4
      • Active, not recruiting
      • CIUSSS de l'Est-de-l'Île-de-Montréal
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N4H4
      • Recruiting
      • Saskatoon Cancer Center
• China
  • Beijing, China, 100730
    • Active, not recruiting
    • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
  • Chongqing, China, 400030
    • Recruiting
    • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510555
      • Recruiting
      • Sun Yat-sen University Cancer Center
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital ， The Affiliated Hospital of Nanjing University Medical School
    • Xuzhou, Jiangsu, China, 221006
      • Active, not recruiting
      • The Affiliated Hospital of Xuzhou Medical University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Active, not recruiting
      • Shandong Provincial Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 301636
      • Recruiting
      • Institute of hematology&blood disease hospital
• Czechia
  • Brno-m?sto
    • Brno, Brno-m?sto, Czechia, 625 00
      • Active, not recruiting
      • Fakultní nemocnice Brno Bohunice
  • Plzeň Region
    • Plzen - Lochotin, Plzeň Region, Czechia, 304 60
      • Recruiting
      • Fakultni Nemocnice Plzen
  • Praha 2
    • Prague, Praha 2, Czechia, 120 00
      • Recruiting
      • Fakultni poliklinika
• Finland
  • Helsinki, Finland, 00029
    • Active, not recruiting
    • Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
• France
  • Paris, France, 75571
    • Recruiting
    • Hôpital Saint Antoine
  • Pierre-Bénite, France, 69495
    • Active, not recruiting
    • Centre Hospitalier Lyon Sud - Service d'Hematologie Clinique
  • Limousin
    • Limoges, Limousin, France, 87042
      • Recruiting
      • Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren
• Germany
  • Berlin, Germany, 12203
    • Active, not recruiting
    • Charité Universitätsmedizin Berlin
  • München, Germany, 81675
    • Recruiting
    • Universitätsklinikum rechts der Isar, Technische Universität München (TUM)
• Greece
  • Attikí
    • Athens, Attikí, Greece, 115 28
      • Active, not recruiting
      • Alexandra General Hospital of Athens
  • Kentrikí Makedonía
    • Thessaloniki, Kentrikí Makedonía, Greece, 546 39
      • Active, not recruiting
      • Theageneio Cancer Hospital of Thessaloniki
• Italy
  • Bologna, Italy, 40138
    • Active, not recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Recruiting
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
• Japan
  • Akita, Japan, 010-8543
    • Recruiting
    • Akita University Hospital
  • Kumamoto, Japan, 860-0008
    • Recruiting
    • National Hospital Organization Kumamoto Medical Center
  • Nagasaki, Japan, 852-8501
    • Recruiting
    • Nagasaki University Hospital
  • Okayama, Japan, 701-1192
    • Active, not recruiting
    • National Hospital Organization Okayama Medical Center
  • Yamagata, Japan, 990-9585
    • Active, not recruiting
    • Yamagata University Hospital
  • Gunma
    • Shibukawa, Gunma, Japan, 377-0280
      • Active, not recruiting
      • National Hospital Organization Shibukawa Medical Center
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Active, not recruiting
      • Tohoku University Hospital
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 66460
      • Active, not recruiting
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
• New Zealand
  • Auckland, New Zealand, 0622
    • Active, not recruiting
    • North Shore Hospital
  • Auckland, New Zealand, 2025
    • Active, not recruiting
    • Aotearoa Clinical Trials
  • Auckland, New Zealand, 1060
    • Active, not recruiting
    • Labtests Auckland Ltd.
  • Hamilton, New Zealand, 3204
    • Active, not recruiting
    • Waikato District Health Board, Waikato Hospital
  • Roslyn, New Zealand, 4414
    • Active, not recruiting
    • Palmerston North Hospital
• Norway
  • Oslo, Norway, 0450
    • Active, not recruiting
    • Oslo Universitetssykehus Ullevål
  • Trondheim, Norway, 7030
    • Active, not recruiting
    • St Olavs hospital
• Poland
  • Bydgoszcz, Poland, 85-168
    • Active, not recruiting
    • Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy Klinika Hematologii
  • Poznan, Poland, 60-569
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Wroclaw, Poland, 50-367
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Girona, Spain, 17007
    • Active, not recruiting
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Madrid, Spain, 28006
    • Recruiting
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28050
    • Active, not recruiting
    • Hospital Universitario Madrid Sanchinarro
  • Salamanca, Spain, 37007
    • Active, not recruiting
    • Hospital Universitario de Salamanca
  • Seville, Spain, 41013
    • Active, not recruiting
    • Hospital Universitario Virgen del Rocio
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
      • Active, not recruiting
      • Hospital Universitari Mutua Terrassa
  • Barcelona [barcelona]
    • L'Hospitalet Del Llobregat, Barcelona [barcelona], Spain, 08908
      • Recruiting
      • Institut Català d'Oncologia - L'Hospitalet
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
  • Other
    • Toledo, Other, Spain, 45007
      • Active, not recruiting
      • Hospital Universitario de Toledo
• Sweden
  • Falun, Sweden, 791 82
    • Active, not recruiting
    • Falu Lasarett
  • Gothenburg, Sweden, 41345
    • Active, not recruiting
    • Sahlgrenska Universitetssjukhuset
  • Skåne LÄN [se-12]
    • Lund, Skåne LÄN [se-12], Sweden, 22185
      • Active, not recruiting
      • Skånes Universitetssjukhus Lund
  • Örebro LÄN [se-18]
    • Örebro, Örebro LÄN [se-18], Sweden, 701 85
      • Active, not recruiting
      • Universitetssjukhuset Orebro
• Taiwan
  • Taichung, Taiwan, 40447
    • Active, not recruiting
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • Active, not recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Active, not recruiting
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Antalya, Turkey (Türkiye), 07070
    • Active, not recruiting
    • Akdeniz Universitesi Hastanesi
  • İ̇zmir
    • Izmir, İ̇zmir, Turkey (Türkiye), 35100
      • Active, not recruiting
      • Ege Universitesi Hastanesi
    • Izmir, İ̇zmir, Turkey (Türkiye), 35340
      • Active, not recruiting
      • Dokuz Eylul Universitesi Hastanesi
• United Kingdom
  • South Glamorgan
    • Cardiff, South Glamorgan, United Kingdom, CF14 4XW
      • Active, not recruiting
      • University Hospital of Wales
• United States
  • California
    • Clovis, California, United States, 93611
      • Active, not recruiting
      • Clovis Community Medical Center
    • Fresno, California, United States, 93721
      • Active, not recruiting
      • Community Regional Medical Center
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • Active, not recruiting
      • UCHealth Poudre Valley Hospital
    • Greeley, Colorado, United States, 80634
      • Active, not recruiting
      • UCHealth Greeley Hospital
  • Florida
    • Aventura, Florida, United States, 33180
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Aventura
    • Coral Springs, Florida, United States, 33065
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Coral Springs
    • Deerfield Beach, Florida, United States, 33442
      • Recruiting
      • University of Miami Hospital and Clinics - Deerfield Beach
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Hollywood
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Hospital and Clinics
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center - Main Campus
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior diagnosis of multiple myeloma as defined by IMWG criteria (Rajkumar et al, 2014).

• Measurable disease based on IMWG criteria as defined by at least 1 of the following:

  • Serum M-protein ≥0.5 g/dL.
  • Urinary M-protein excretion ≥200 mg/24 hours.
  • Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
• Prior anti-multiple myeloma therapy including treatment with lenalidomide.
• ECOG performance status ≤2.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
• Not pregnant and willing to use contraception.

Exclusion Criteria:

• Smoldering multiple myeloma.
• Plasma cell leukemia.
• Amyloidosis.
• POEMS Syndrome.
• Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease.
• Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection.
• Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Previous treatment with a BCMA-directed therapy.
• Live attenuated vaccine within 4 weeks of the first dose of study intervention.
• Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Safety Lead-In Dose Escalation: Elranatamab + Daratumumab	Drug: Elranatamab; subcutaneous; Other Names: PF-06863135; Drug: Daratumumab; Daratumumab / hyaluronidase, subcutaneous; Other Names: Darzalex Faspro; Darzalex solution for injection
Experimental: Part 2 Randomized Arm A: Elranatamab	Drug: Elranatamab; subcutaneous; Other Names: PF-06863135
Experimental: Part 2 Randomized Arm B: Elranatamab + Daratumumab	Drug: Elranatamab; subcutaneous; Other Names: PF-06863135; Drug: Daratumumab; Daratumumab / hyaluronidase, subcutaneous; Other Names: Darzalex Faspro; Darzalex solution for injection
Active Comparator: Part 2 Randomized Arm C: Daratumumab + Pomalidomide + Dexamethasone	Drug: Daratumumab; Daratumumab / hyaluronidase, subcutaneous; Other Names: Darzalex Faspro; Darzalex solution for injection; Drug: Pomalidomide; oral; Other Names: Pomalyst, Imnovid; Drug: Dexamethasone; oral
Experimental: Part 3 Arm D: Elranatamab	Drug: Elranatamab; subcutaneous; Other Names: PF-06863135
Experimental: Part 3 Arm E: Elranatamab + Daratumumab	Drug: Elranatamab; subcutaneous; Other Names: PF-06863135; Drug: Daratumumab; Daratumumab / hyaluronidase, subcutaneous; Other Names: Darzalex Faspro; Darzalex solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1 Safety Lead-In: Incidence of dose limiting toxicities	First 42 days after first elranatamab dose
Part 2 Randomized: Progression free survival per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months
Part 3: Frequency of treatment-emergent adverse events	First 84 days after first elranatamab dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of treatment-emergent adverse events	From date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy.
Frequency of abnormal laboratory results	From date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy.
Rate of Grade ≥2 cytokine release syndrome	First 28 days after first elranatamab dose
Elranatamab pharmacokinetics by pre- and post-dose concentrations	From date of first dose through up to 14 days after date of last dose of elranatamab
Elranatamab immunogenicity by anti-drug antibodies against elranatamab	From date of first dose through up to 14 days after date of last dose of elranatamab
Daratumumab pharmacokinetics by pre-dose concentrations	From date of first dose through up to 14 days after date of last dose of daratumumab
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30	From date of informed consent through up to 35 days after date of last dose of study intervention
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20	From date of informed consent through up to 35 days after date of last dose of study intervention
Part 1 Safety Lead-In: Progression free survival per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Overall survival	From date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Objective response rate per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Duration of response per International Myeloma Working Group criteria	From date of confirmed objective response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Time to response per International Myeloma Working Group criteria	From date of randomization to date of confirmed objective response, assessed up to 51 months
Complete response rate per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Duration of complete response per International Myeloma Working Group criteria	From date of confirmed complete response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Minimal residual disease negativity rate per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Sustained minimal residual disease negativity rate per International Myeloma Working Group criteria	From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Progression free survival on next-line treatment per International Myeloma Working Group criteria	From date of randomization to date of second objective disease progression, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Estimated): April 27, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Multiple myeloma; Pomalidomide; Daratumumab; PF-06863135; BCMA; Elranatamab; Bispecific antibody; B-Cell Maturation Antigen; BCMA-CD3 bispecific antibody; Relapsed multiple myeloma; Refractory multiple myeloma; MagnetisMM-5
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Therapeutics; Drug Administration Routes; Drug Therapy; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; Injections; pomalidomide; daratumumab
• Other Study ID Numbers: C1071005; MAGNETISMM-5 (Other Identifier: Alias Study Number); 2023-509208-14-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No