MAGNETISMM-5: MagnetisMM-5: Study of Elranatamab (PF-06863135) Monotherapy and Elranatamab + Daratumumab Versus Daratumumab + Pomalidomide + Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05020236

Collaborator

(none)

589

Enrollment

124

Locations

Arms

52.7

Anticipated Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether the BCMA-CD3 bispecific antibody elranatamab, alone and/or in combination with the anti-CD38 monoclonal antibody, daratumumab, can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone. People with multiple myeloma who have received previous treatment including lenalidomide and a proteasome inhibitor 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 compare the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab compared to daratumumab, pomalidomide, and dexamethasone. Participants in both parts of 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Elranatamab Drug: Daratumumab Drug: Pomalidomide Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

589 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 4, 2021

Anticipated Primary Completion Date :

Oct 26, 2024

Anticipated Study Completion Date :

Feb 24, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 32 months]

Secondary Outcome Measures

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 32 months]
Overall survival [From date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first, assessed up to 32 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 32 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 32 months]
Time to response per International Myeloma Working Group criteria [From date of randomization to date of confirmed objective response, assessed up to 32 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 32 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 32 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 32 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 32 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 32 months]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 and a proteasome inhibitor.
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.
Anti-CD38-directed therapy within 6 months preceding the first dose of treatment in this study.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
2	St Vincent's Hospital (Melbourne)	Fitzroy	Victoria	Australia	3065
3	The Alfred Hospital	Melbourne	Victoria	Australia	3004
4	Universitätsklinikum Krems	Krems	Niederösterreich	Austria	3500
5	CHU UCL Namur (site Godinne)	Yvoir	Namur	Belgium	5530
6	Tom Baker Cancer Center	Calgary	Alberta	Canada	T2N 4N2
7	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
8	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
9	Victoria Building - QEII	Halifax	Nova Scotia	Canada	B3H 2Y9
10	Hamilton Health Sciences-Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V5C2
11	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
12	Peking University Third Hospital	Beijing	Beijing	China	100191
13	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510515
14	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510555
15	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
16	Jinan Central Hospital	Jinan	Shandong	China	250013
17	Institute of hematology&blood disease hospital	Tianjin	Tianjin	China	300020
18	Beijing Boren Hospital	Beijing		China	100070
19	Chongqing University Cancer Hospital	Chongqing		China	400030
20	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
21	Tampereen yliopistollinen sairaala	Tampere	Pirkanmaa	Finland	33520
22	Oulun yliopistollinen sairaala	Oulu	Pohjois-pohjanmaa	Finland	90220
23	Turku University Hospital	Turku	Varsinais-suomi	Finland	20520
24	Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)	Helsinki		Finland	00029
25	Tampereen yliopistollinen sairaala	Tampere		Finland	33520
26	Hopital Claude Huriez - CHU de Lille	Lille	Nord	France	59000
27	Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu	Nantes		France	44093
28	Hôpital Saint Antoine	Paris Cedex 12		France	75571
29	Hopital Necker	Paris		France	75015
30	CHU de Poitiers, Hôpital de la Milétrie, Pôle Régional de Cancérologie	Poitiers Cedex		France	86021
31	Universitätsklinikum Würzburg	Würzburg	Bayern	Germany	97080
32	Klinikum Chemnitz gGMbH	Chemnitz		Germany	09116
33	Evangelismos General Hospital of Athens	Athens	Attikí	Greece	106 76
34	Evangelismos Hospital	Athens	Attikí	Greece	106 76
35	Alexandra General Hospital of Athens	Athens	Attikí	Greece	115 28
36	Theageneio Cancer Hospital of Thessaloniki	Thessaloniki	Kentrikí Makedonía	Greece	546 39
37	University General Hospital of Ioannina	Ioannina		Greece
38	Rajiv Gandhi Cancer Institute & Research Centre	New Delhi	Delhi	India	110085
39	Rajiv Gandhi Cancer Institute And Research Centre	New Delhi	Delhi	India	110085
40	Artemis Hospital	Gurugram	Haryana	India	122001
41	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra	India	411 004
42	Christian Medical College Vellore	Vellore	Tamil NADU	India	632004
43	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Lazio	Italy	00168
44	Ospedale San Martino	Genova	Liguria	Italy	16132
45	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Lombardia	Italy	20122
46	Policlinico "G. Rodolico"	Catania	Sicilia	Italy	95123
47	IRCCS - AOU di Bologna	Bologna		Italy	40138
48	AOU Policlinico Umberto I	Roma		Italy	00161
49	Fondazione Policlinico Universitario Agostino Gemelli	Roma		Italy	00168
50	Nagoya City University Hospital	Nagoya	Aichi	Japan	467-8602
51	National Hospital Organization Shibukawa Medical Center	Shibukawa	Gunma	Japan	377-0280
52	Iwate Medical University Hospital	Shiwa-gun Yahaba-cho	Iwate	Japan	028-3695
53	Iwate Medical University Hospital	Yahaba-cho, Shiwa-gun	Iwate	Japan	028-3695
54	Hamamatsu University Hospital	Hamamatsu	Shizuoka	Japan	431-3192
55	Shizuoka Cancer Center	Sunto-gun	Shizuoka	Japan	411-8777
56	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo	Japan	150-8935
57	Akita University Hospital	Akita		Japan	010-8543
58	National Hospital Organization Kumamoto Medical Center	Kumamoto		Japan	860-0008
59	National Hospital Organization Okayama Medical Center	Okayama		Japan	701-1192
60	Osaka Metropolitan University Hospital	Osaka		Japan	545-8586
61	Tokushima University Hospital	Tokushima		Japan	770-8503
62	Yamagata University Hospital	Yamagata		Japan	990-9585
63	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
64	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeonranamdo	Korea, Republic of	58128
65	Pusan National University Hospital	Busan	Pusan-kwangyǒkshi	Korea, Republic of	49241
66	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [seoul]	Korea, Republic of	03080
67	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [seoul]	Korea, Republic of	06351
68	The Catholic Univ. of Korea Seoul St. Mary's Hospital	Seoul	Seoul-teukbyeolsi [seoul]	Korea, Republic of	06591
69	Kyungpook National University Hospital	Daegu	Taegu-kwangyǒkshi	Korea, Republic of	41944
70	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
71	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
72	Asan Medical Center	Seoul		Korea, Republic of	05505
73	Erasmus Universitair Medisch Centrum	Rotterdam	Zuid-holland	Netherlands	3015 GD
74	Palmerston North Hospital	Palmerston North	Manawatu	New Zealand	4414
75	Palmerston North Hospital	Roslyn		New Zealand	4414
76	Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy Klinika Hematologii	Bydgoszcz		Poland	85-168
77	Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
78	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
79	Pratia Onkologia Katowice	Katowice		Poland	40-519
80	Centrum Medyczne Pratia Poznan	Skorzewo		Poland	60-185
81	Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku	Wroclaw		Poland	50-367
82	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	A Coruna	Spain	15706
83	Institut Català d'Oncologia - L'Hospitalet	L'Hospitalet Del Llobregat	Barcelona [barcelona]	Spain	08908
84	Hospital Universitario Mutua Terrassa	Terrassa	Barcelona	Spain	08221
85	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
86	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
87	Hospital Universitario de Toledo	Toledo	Other	Spain	45007
88	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
89	Hospital Clinic Barcelona	Barcelona		Spain	08036
90	Hospital Universitario Reina Sofía	Cordoba		Spain	14004
91	Hospital Universitari De Girona Doctor Josep Trueta	Girona		Spain	17007
92	Hospital Universitario La Princesa	Madrid		Spain	28006
93	Hospital de Madrid Sanchinarro	Madrid		Spain	28050
94	Hospital Universitario de Salamanca	Salamanca		Spain	37007
95	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
96	Hospital Universitario y Politecnico La Fe	Valencia		Spain	46026
97	Helsingborgs Lasarett	Helsingborg	Skåne LÄN [se-12]	Sweden	251 87
98	Skånes Universitetssjukhus Lund	Lund	Skåne LÄN [se-12]	Sweden	22185
99	Södra Älvsborg Sjukhus	Borås		Sweden	501 82
100	Falu Lasarett	Falun		Sweden	791 82
101	Sahlgrenska Universitetssjukhuset	Göteborg		Sweden	41345
102	Universitetssjukhuset Örebro	Örebro	Örebro LÄN [se-18]	Sweden	701 85
103	Universitetssjukhuset i Linköping	Linköping	Östergötlands LÄN [se-05]	Sweden	581 85
104	Chang Gung Memorial Hospital at Kaohsiung	Kaohsiung		Taiwan	83301
105	China Medical University Hospital	Taichung		Taiwan	40447
106	National Cheng-Kung Uni. Hosp.	Tainan		Taiwan	704
107	National Taiwan University Hospital	Taipei		Taiwan	10002
108	Taipei Veterans General Hospital	Taipei		Taiwan	11217
109	Sisli Florence Nightingale Hastanesi	İstanbul / Şişli	İ̇stanbul	Turkey	34381
110	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul	İ̇stanbul	Turkey	34093
111	Medipol Mega Universite Hastanesi	İstanbul	İ̇stanbul	Turkey	34214
112	Acibadem Universitesi Atakent Hastanesi	Istanbul	İ̇stanbul	Turkey	34303
113	Ege Universitesi Hastanesi	İzmir	İ̇zmir	Turkey	35100
114	Dokuz Eylul Universitesi Hastanesi	İzmir	İ̇zmir	Turkey	35340
115	Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi	Adana		Turkey	01240
116	Ankara Universitesi Tip Fakultesi Hastanesi	Ankara		Turkey	06100
117	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastırma Hastanesi	Ankara		Turkey	06200
118	Akdeniz Universitesi Hastanesi	Antalya		Turkey	07070
119	Aydın Adnan Menderes Universitesi Hastanesi	Aydin		Turkey	09100
120	Gaziantep Universitesi Sahinbey Arastirma ve Uygulama Hastanesi	Gaziantep		Turkey	27310
121	Özel Anadolu Sağlık Merkezi	Kocaeli		Turkey	41400
122	Inonu Universitesi Turgut Ozal Tıp Merkezi	Malatya		Turkey	44280
123	Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LE
124	University Hospital of Wales	Cardiff	South Glamorgan	United Kingdom	CF14 4XW