Clinical trial NCT05623020: A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, Lenalidomide or Elranatamab and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant
Official title: MAGNETISMM-6: AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE OR ELRANATAMAB + LENALIDOMIDE VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Elranatamab
PF-06863135
B-Cell Maturation Antigen
Daratumumab
Lenalidomide
Multiple myeloma
MagnetisMM-6
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-11-21
Enrollment: 966
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide or Elranatamab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Lenalidomide and Dexamethasone in people with multiple myeloma.

There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide or elranatamab and lenalidomide compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple myeloma (MM) 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;
  * Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (\<0.26 or \>1.65).
* Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age \<65 years with comorbidities impacting the possibility of transplant.
* Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age \<65 years with comorbidities impacting the possibility of transplant
* ECOG performance status ≤2.
* Not pregnant and willing to use contraception
* For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

Exclusion Criteria:

* Smoldering Multiple Myeloma.
* Monoclonal gammopathy of undetermined significance.
* Waldenströms Macroglobulinemia
* Plasma cell leukemia.
* Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
* Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
* For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
* For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, up to 4 days of 40 mg dexamethasone or equivalent before the first dose of study intervention).
* Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
* Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Primary outcomes:
measure: Part 1 Dose Limiting Toxicity
timeFrame: From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide
measure: Part 2: Progression free survival by blinded independent central review
timeFrame: From randomization up to 79 months.
measure: Part 2: Minimal Residual Disease negativity rate
timeFrame: At 12 months after randomization
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of randomization up to 79 months
measure: Overall minimal residual disease negativity rate
timeFrame: From date of randomization up to 79 months
measure: Sustained MRD negativity rate (Part 2)
timeFrame: From date of randomization up to 79 months
measure: Duration of minimal residual disease negativity (Part 2)
timeFrame: From date of minimal residual disease negative status up to 79 months
measure: PFS by investigator
timeFrame: From date of randomization up to 79 months
measure: PFS2 by investigator (Part 2)
timeFrame: From the date of randomization up to 79 months
measure: Objective Response Rate
timeFrame: From the date of randomization up to 79 months
measure: Complete Response Rate
timeFrame: From the date of randomization up to 79 months
measure: Time to Response
timeFrame: From the date of randomization to date of confirmed objective response up to 79 months
measure: Duration of Response
timeFrame: From the date of confirmed objective response up to 79 months
measure: Duration of Complete Response
timeFrame: From the date of confirmed complete response up to 79 months
measure: Frequency of treatment-emergent adverse events
timeFrame: From the date of first dose of study intervention up to 79 months
measure: Frequency of abnormal laboratory results
timeFrame: From the date of first dose of study intervention up to 79 months
measure: Pharmacokinetics of elranatamab when used in the elranatamab + daratumumab + lenalidomide or elranatamab + lenalidomide combinations
timeFrame: From date of first dose of study intervention up to 79 months
measure: Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab
timeFrame: From date of first dose of study intervention up to 79 months
measure: Pharmacokinetics of daratumumab and lenalidomide when used in the elranatamab+daratumumab+lenalidomide or elranatamab+lenalidomide combinations (Part 1)
timeFrame: From date of first dose of study intervention up to 79 months
measure: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (Part 2)
timeFrame: From date the informed consent is signed up to 79 months
measure: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 (Part 2)
timeFrame: From date the informed consent is signed up to 79 months
Other outcomes:
Locations:
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Epworth Freemasons
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Bohunice
state: Brno-město
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
state: Moravskoslezský KRAJ
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE
state: Haute-garonne
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
state: Vienne
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden-württemberg
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
state: Attikí
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
state: Attikí
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
state: Ípeiros
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
state: Hadarom
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center
state: Hamerkaz
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
state: Hamerkaz
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Tell Abīb
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Piacenza
country: Italy
facility: AUSL di Piacenza
state: Emilia-romagna
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
state: Emilia-romagna
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
state: FG
city: Aviano
country: Italy
facility: Cro-Irccs
state: Friuli-venezia Giulia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
state: Piemonte
city: Palermo
country: Italy
facility: A.O.U. Policlinico Paolo Giaccone
state: Sicilia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS
city: Pescara
country: Italy
facility: ASL PESCARA-Presidio Ospedaliero Pescara
city: Roma
country: Italy
facility: AOU Policlinico Umberto I
city: Yoshida-gun
country: Japan
facility: University of Fukui Hospital
state: Fukui
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Yahaba-cho
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Nagaizumi-cho
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon-gwangyeoksi [incheon]
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeonranamdo
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, locatie Dordwijk
state: Zuid-holland
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
state: Dolnośląskie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
state: Śląskie
city: Badalona
country: Spain
facility: Institut Català d'Oncologia (ICO) - Badalona
state: Barcelona [barcelona]
city: L'Hospitalet Del Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [cataluña]
city: Girona
country: Spain
facility: Institut Català d'Oncologia (ICO) - Girona
state: Girona [gerona]
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
state: Madrid, Comunidad DE
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
state: València
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: