Clinical trial NCT04649359: MagnetisMM-3: Study Of Elranatamab (PF-06863135) Monotherapy in Participants With Multiple Myeloma Who Are Refractory to at Least One PI, One IMiD and One Anti-CD38 mAb
Official title: MAGNETISMM-3 AN OPEN-LABEL, MULTICENTER, NON-RANDOMIZED PHASE 2 STUDY OF ELRANATAMAB (PF-06863135) MONOTHERAPY IN PARTICIPANTS WITH MULTIPLE MYELOMA WHO ARE REFRACTORY TO AT LEAST ONE PROTEASOME INHIBITOR, ONE IMMUNOMODULATORY DRUG AND ONE ANTI-CD38 ANTIBODY
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Myeloma
Multiple Myeloma
relapsed Multiple Myeloma
refractory Multiple Myeloma
PF-06863135
BCMA
bispecific
bispecific antibody
BCMA-CD3 bispecific
Elranatamab
MagnetisMM-3
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-12-02
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate whether single-agent Elranatamab (PF-06863135) can provide clinical benefit in participants with relapsed/refractory multiple myeloma. Elranatamab is a bispecific antibody: binding of Elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014)
* Measurable disease, as defined by at least 1 of the following:

  1. Serum M-protein \>0.5 g/dL by SPEP
  2. Urinary M-protein excretion \>200 mg/24 hours by UPEP
  3. Serum immunoglobulin FLC≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio
* Refractory to at least one IMiD
* Refractory to at least one PI
* Refractory to at least one anti-CD38 antibody
* Relapsed/refractory to last anti-myeloma regimen
* Cohort A: has not received prior BCMA-directed therapy
* Cohort B: has received prior BCMA-directed therapy (ADC or CAR T cells)
* 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
* Active Plasma cell leukemia
* Amyloidosis
* POEMS syndrome
* Stem cell transplant within 12 weeks prior to enrollment
* Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection
* Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
* Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)

Primary outcomes:
measure: Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months)
Secondary outcomes:
measure: Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants With Extramedullary Disease (EMD) at Baseline
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months)
measure: Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants Without EMD at Baseline
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months)
measure: Duration of Response (DOR) as Per IMWG Criteria by BICR
timeFrame: From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Duration of Response as Per IMWG Criteria by Investigator Assessment
timeFrame: From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Complete Response Rate (CRR) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
measure: Complete Response Rate as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
measure: Objective Response Rate as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
measure: Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR
timeFrame: From first documentation of sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Duration of Complete Response (DOCR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From first documentation of objective sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Progression Free Survival (PFS) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Progression Free Survival (PFS) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
measure: Overall Survival (OS)
timeFrame: From the date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive (up to approximately 20.14 months)
measure: Time-to-Response (TTR) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months)
measure: Time-to-Response (TTR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
measure: Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
measure: Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Laboratory Parameters by NCI CTCAE v 5.0
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
measure: Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
measure: Number of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
measure: Serum Concentration of Elranatamab
timeFrame: Pre-dose on Day 1 of Cycle 4 and Pre-dose on Day 1 of Cycle 7
measure: Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab
timeFrame: From the date of first dose up to 20.14 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Health - Chao Family Comprehensive Cancer Center
state: California
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute @ Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Group
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Chicago performing research at Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa - Holden Comprehensive Cancer Center
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Louisville
country: United States
facility: Norton Women's and Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: St. Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: St Francis Eastside
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: East Melbourne
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital (Melbourne)
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Antwerpen
country: Belgium
facility: ZNA-Middelheim
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Yvoir
country: Belgium
facility: CHU UCL Namur site Godinne
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Montreal
country: Canada
facility: CIUSSS-EMTL, Installation Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre - Glen Site
state: Quebec
city: Lille
country: France
facility: CHU de Lille - Hopital Claude Huriez
city: Nantes Cedex 1
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Paris Cedex 12
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud - Service d'Hematologie Clinique
city: Poitiers Cedex
country: France
facility: CHU de Poitiers, Pôle Régional de Cancérologie
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg - Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinik Schleswig-Holstein
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Kobe-city
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Yahaba-cho
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
state: Tokyo
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: A Coruna
city: Badalona
country: Spain
facility: Institut Catala d' Oncologia. Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: