A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant

Multiple Myeloma Clinical Trial

— MagnetisMM-6  

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 VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY-DIAGNOSED MULTIPLE MYELOMA

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05623020
• Other study ID #: C1071006
• Secondary ID: 2021-000803-20
• Status: Recruiting
• Phase: Phase 3
• Start date: November 10, 2022
• Est. completion date: November 29, 2031

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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 when administered in combination with daratumumab and 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 compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 966
• Est. completion date: November 29, 2031
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Elranatamab
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Daratumumab
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Lenalidomide
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Dexamethasone
Randomized

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Epworth Freemasons	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Epworth Hospital	Richmond	Victoria
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Czechia	Fakultní nemocnice Brno Bohunice	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava	Moravskoslezský KRAJ
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu	Nantes
France	Centre Hospitalier Universitaire de Poitiers	Poitiers	Vienne
France	Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE	Toulouse	Haute-garonne
Germany	Klinikum Chemnitz	Chemnitz
Germany	Universitaetsklinikum Tuebingen	Tübingen	Baden-württemberg
Greece	Alexandra General Hospital of Athens	Athens	Attikí
Greece	Evangelismos General Hospital of Athens	Athens	Attikí
Greece	University Hospital of Ioannina	Ioannina	Ípeiros
Israel	Soroka Medical Center	Be'er Sheva	Hadarom
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Rabin Medical Center	Petah-Tikva	Hamerkaz
Israel	The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric	Ramat Gan	Hamerkaz
Israel	Sourasky Medical Center	Tel Aviv	Tell Abib
Italy	Istituto Europeo di Oncologia IRCCS	Milano
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	A.O.U. Policlinico Paolo Giaccone	Palermo	Sicilia
Italy	ASL PESCARA-Presidio Ospedaliero Pescara	Pescara
Italy	AUSL di Piacenza	Piacenza	Emilia-romagna
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Ospedale Santa Maria delle Croci	Ravenna	Emilia-romagna
Italy	AOU Policlinico Umberto I	Roma
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	FG
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino	Piemonte
Japan	University of Fukui Hospital	Eiheiji-cho,Yoshida-gun	Fukui
Japan	Kyushu University Hospital	Fukuoka
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Shizuoka Cancer Center	Nagaizumi-cho,Sunto-gun	Shizuoka
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Tohoku University Hospital	Sendai-shi	Miyagi
Japan	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo
Japan	Iwate Medical University Hospital	Shiwa-gun Yahaba-cho	Iwate
Japan	Iwate Medical University Hospital	Yahaba-cho, Shiwa-gun	Iwate
Japan	Yamagata University Hospital	Yamagata
Japan	University of Fukui Hospital	Yoshida-gun	Fukui
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeonranamdo
Korea, Republic of	Gachon University Gil Medical Center	Namdong-gu	Incheon-gwangyeoksi [incheon]
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [seoul]
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Pratia Onkologia Katowice	Katowice	Slaskie
Poland	Centrum Medyczne Pratia Poznan	Skorzewo	Wielkopolskie
Poland	MTZ Clinical Research Powered by Pratia	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Spain	Institut Català d'Oncologia (ICO) - Badalona	Badalona	Barcelona [barcelona]
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [cataluña]
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Institut Català d'Oncologia (ICO) - Girona	Girona	Girona [gerona]
Spain	Institut Català d'Oncologia - L'Hospitalet	L'Hospitalet Del Llobregat	Barcelona [barcelona]
Spain	Clinica Universidad de Navarra	Madrid	Madrid, Comunidad DE
Spain	Hospital La Princesa	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Doctor Peset	Valencia	València
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Australia,  Canada,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Dose Limiting Toxicity		From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab 76 with daratumumab and lenalidomide
Primary	Part 2: Progression free survival by blinded independent central review		From randomization up to 73 months.
Primary	Part 2: Sustained minimal residual disease negativity rate		For at least 12 months after date of initial MRD-negative status
Secondary	Overall Survival		From date of randomization up to 73 months
Secondary	Overall minimal residual disease negativity rate		From date of randomization up to 73 months
Secondary	Duration of minimal residual disease negativity (Part 2)		From date of minimal residual disease negative status up to 73 months
Secondary	PFS by investigator		From date of randomization up to 73 months
Secondary	PFS2 by investigator (Part 2)		From the date of randomization up to 73 months
Secondary	Objective Response Rate		From the date of randomization up to 73 months
Secondary	Complete Response Rate		From the date of randomization up to 73 months
Secondary	Time to Response		From the date of randomization to date of confirmed objective response up to 73 months
Secondary	Duration of Response		From the date of confirmed objective response up to 73 months
Secondary	Duration of Complete Response		From the date of confirmed complete response up to 73 months
Secondary	Frequency of treatment-emergent adverse events		From the date of first dose of study intervention up to 73 months
Secondary	Frequency of abnormal laboratory results		From the date of first dose of study intervention up to 73 months
Secondary	Elranatamab pharmacokinetics by pre-dose concentrations when used with lenalidomide and daratumumab	Pharmacokinetics of elranatamab (trough concentrations of elranatamab)	From date of first dose of study intervention up to 73 months
Secondary	Elranatamab pharmacokinetics by post-dose concentrations when used with lenalidomide and daratumumab	Pharmacokinetics of elranatamab (post-dose serum concentrations of elranatamab)	From date of first dose of study intervention up to 73 months
Secondary	Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab	Immunogenicity of elranatamab	From date of first dose of study intervention up to 73 months
Secondary	Titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab	Immunogenicity of elranatamab	From date of first dose of study intervention up to 73 months
Secondary	Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20	Higher scores on the functioning subscales (body image, future perspective) represent higher levels of functioning, whereas higher scores on the symptom subscales (disease symptoms, side effects) represent a greater presence of symptoms	From date the informed consent is signed up to 73 months
Secondary	Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30	Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the symptom scales/items represent a greater presence of symptoms.	From date the informed consent is signed up to 73 months
Secondary	Part 1: Daratumumab and lenalidomide pharmacokinetics by pre-dose concentrations in combination with elranatamab	Pharmacokinetics of daratumumab and lenalidomide (trough concentrations of daratumumab and lenalidomide)	From date of first dose of study intervention up to 73 months

External Links

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