A Study to Investigate the Clinical Benefit of Isatuximab in Combination With Bortezomib, Lenalidomide and Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant (IMROZ)

A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

Primary Objective:

-To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in participants with newly diagnosed multiple myeloma (NDMM) not eligible for transplant.

Secondary Objectives:

• To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms:
• Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria.
• Minimal residual disease (MRD) negativity rate in participants with CR.
• Very good partial response or better rate, as defined by the IMWG criteria.
• Overall survival (OS).
• To evaluate the overall response rate (ORR) as per IMWG criteria.
• To evaluate the time to progression (TTP) overall and by MRD status.
• To evaluate PFS by MRD status.
• To evaluate the duration of response (DOR) overall and by MRD status.
• To evaluate time to first response (TT1R).
• To evaluate time to best response (TTBR).
• To evaluate progression-free survival on next line of therapy (PFS2).
• To evaluate the sustained MRD negativity >12 months rate.
• To evaluate safety.
• To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only).
• To evaluate the immunogenicity of isatuximab in participants receiving isatuximab (IVRd and crossover arms).
• To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Study Overview

• Status: Active, not recruiting
• Conditions: Plasma Cell Myeloma
• Intervention / Treatment: Drug: Isatuximab SAR650984; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Detailed Description

The duration of the study for each participant will include a screening period of up to 4 weeks, an induction period of 24 weeks (4 cycles with a duration of 42 ± 3 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 3 days during the continuous treatment and crossover periods.

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Investigational Site Number : 0360003
    • Waratah, New South Wales, Australia, 2298
      • Investigational Site Number : 0360001
    • Wollongong, New South Wales, Australia, 2500
      • Investigational Site Number : 0360002
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Investigational Site Number : 0360007
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Investigational Site Number : 0360005
    • Heidelberg West, Victoria, Australia, 3081
      • Investigational Site Number : 0360004
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Investigational Site Number : 0360006
    • West Perth, Western Australia, Australia, 6005
      • Investigational Site Number : 0360008
• Belgium
  • Liège, Belgium, 4000
    • Investigational Site Number : 0560001
• China
  • Beijing, China, 100034
    • Investigational Site Number : 1560002
  • Beijing, China, 100191
    • Investigational Site Number : 1560003
  • Changchun, China, 130021
    • Investigational Site Number : 1560008
  • Fuzhou, China, 350001
    • Investigational Site Number : 1560007
  • Guangzhou, China, 510060
    • Investigational Site Number : 1560009
  • Guangzhou, China, 510080
    • Investigational Site Number : 1560006
  • Hangzhou, China, 310003
    • Investigational Site Number : 1560005
  • Hangzhou, China, 310003
    • Investigational Site Number : 1560014
  • Nanjing, China, 210029
    • Investigational Site Number : 1560004
  • Shanghai, China, 200025
    • Investigational Site Number : 1560013
  • Shenyang, China, 110022
    • Investigational Site Number : 1560011
  • Tianjin, China, 300020
    • Investigational Site Number : 1560001
  • Wuhan, China, 430022
    • Investigational Site Number : 1560012
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number : 2030002
  • Hradec Králové, Czechia, 50005
    • Investigational Site Number : 2030007
  • Olomouc, Czechia, 77900
    • Investigational Site Number : 2030004
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number : 2030003
  • Pilsen, Czechia, 30599
    • Investigational Site Number : 2030006
  • Prague, Czechia, 12808
    • Investigational Site Number : 2030001
• Denmark
  • Aalborg, Denmark, 9000
    • Investigational Site Number : 2080002
  • Aarhus N, Denmark, 8200
    • Investigational Site Number : 2080003
  • Odense C, Denmark, 5000
    • Investigational Site Number : 2080004
• France
  • Bayonne, France, 64100
    • Investigational Site Number : 2500011
  • Caen, France, 14033
    • Investigational Site Number : 2500007
  • Dijon, France, 21000
    • Investigational Site Number : 2500009
  • La Roche-sur-Yon, France, 85925
    • Investigational Site Number : 2500008
  • Lille, France, 59037
    • Investigational Site Number : 2500001
  • Nantes, France, 44093
    • Investigational Site Number : 2500003
  • Paris, France, 75012
    • Investigational Site Number : 2500012
  • Pessac, France, 33600
    • Investigational Site Number : 2500002
  • Pierre-Bénite, France, 69495
    • Investigational Site Number : 2500006
  • Poitiers, France, 86021
    • Investigational Site Number : 2500005
  • Toulouse, France, 31059
    • Investigational Site Number : 2500004
  • Vandœuvre-lès-Nancy, France, 54511
    • Investigational Site Number : 2500010
• Germany
  • Berlin, Germany, 13125
    • Investigational Site Number : 2760003
  • Frankfurt am Main, Germany, 60590
    • Investigational Site Number : 2760004
  • Heidelberg, Germany, 69120
    • Investigational Site Number : 2760001
  • Tübingen, Germany, 72076
    • Investigational Site Number : 2760005
• Greece
  • Athens, Greece, 11528
    • Investigational Site Number : 3000001
  • Athens, Greece, 10676
    • Investigational Site Number : 3000003
  • Thessaloniki, Greece, 57010
    • Investigational Site Number : 3000002
• Italy
  • Ancona, Italy, 60032
    • Investigational Site Number : 3800005
  • Bergamo, Italy, 24127
    • Investigational Site Number : 3800003
  • Bologna, Italy, 40138
    • Investigational Site Number : 3800001
  • Brescia, Italy, 25123
    • Investigational Site Number : 3800004
  • Torino, Italy, 10126
    • Investigational Site Number : 3800002
• Japan
  • Yamagata, Japan, 990-9585
    • Investigational Site Number : 3920010
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Investigational Site Number : 3920007
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 311-3193
      • Investigational Site Number : 3920004
  • Kanagawa
    • Konan-ku, Yokohama-shi, Kanagawa, Japan, 234-0054
      • Investigational Site Number : 3920008
  • Kumamoto
    • Kumamoto, Kumamoto, Japan, 860-8556
      • Investigational Site Number : 3920003
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
      • Investigational Site Number : 3920009
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 701-1192
      • Investigational Site Number : 3920005
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Investigational Site Number : 3920006
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Investigational Site Number : 3920001
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Investigational Site Number : 3920002
• Lithuania
  • Klaipėda, Lithuania, LT-92288
    • Investigational Site Number : 4400002
  • Vilnius, Lithuania, 08661
    • Investigational Site Number : 4400001
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Investigational Site Number : 4840001
• New Zealand
  • Auckland, New Zealand, 2025
    • Investigational Site Number : 5540001
  • Auckland
    • Takapuna, Auckland, New Zealand, 1309
      • Investigational Site Number : 5540002
  • Waikato Region
    • Hamilton, Waikato Region, New Zealand, 3204
      • Investigational Site Number : 5540003
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-631
      • Investigational Site Number : 6160004
  • Lódzkie
    • Lodz, Lódzkie, Poland, 93-510
      • Investigational Site Number : 6160003
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Investigational Site Number : 6160001
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Investigational Site Number : 6160002
• Portugal
  • Braga, Portugal, 4710-243
    • Investigational Site Number : 6200002
  • Coimbra, Portugal, 3000-075
    • Investigational Site Number : 6200006
  • Lisbon, Portugal, 1070
    • Investigational Site Number : 6200001
  • Porto, Portugal, 4200-319
    • Investigational Site Number : 6200005
  • Porto, Portugal, 4200
    • Investigational Site Number : 6200003
• Russia
  • Moscow, Russia, 125284
    • Investigational Site Number : 6430001
  • Moscow, Russia, 129301
    • Investigational Site Number : 6430002
• Spain
  • Madrid, Spain, 28034
    • Investigational Site Number : 7240003
  • Murcia, Spain, 30008
    • Investigational Site Number : 7240001
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240005
    • Barcelona, Barcelona [Barcelona], Spain, 08041
      • Investigational Site Number : 7240004
• Sweden
  • Lund, Sweden, 221 85
    • Investigational Site Number : 7520002
  • Stockholm, Sweden, 14186
    • Investigational Site Number : 7520001
• Taiwan
  • Changhua, Taiwan, 500
    • Investigational Site Number : 1580003
  • Taichung, Taiwan, 40447
    • Investigational Site Number : 1580002
  • Taipei, Taiwan, 100
    • Investigational Site Number : 1580001
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Investigational Site Number : 7920006
  • Ankara, Turkey (Türkiye), 06620
    • Investigational Site Number : 7920001
  • Ankara, Turkey (Türkiye), 06500
    • Investigational Site Number : 7920007
  • Istanbul, Turkey (Türkiye), 34390
    • Investigational Site Number : 7920002
  • Izmir, Turkey (Türkiye), 35340
    • Investigational Site Number : 7920003
  • Izmir, Turkey (Türkiye), 35040
    • Investigational Site Number : 7920004
  • Kayseri, Turkey (Türkiye), 38039
    • Investigational Site Number : 7920005
  • Samsun, Turkey (Türkiye), 55139
    • Investigational Site Number : 7920008
• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Investigational Site Number: 8400006
    • St. Petersburg, Florida, United States, 33705
      • Investigational Site Number: 8400004
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Investigational Site Number: 8400007
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Investigational Site Number: 8400005
  • Texas
    • Houston, Texas, United States, 77030
      • Investigational Site Number: 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion criteria :

• Multiple myeloma (IMWG criteria).
• Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants < 65 years with comorbidities impacting possibility of transplant.
• Evidence of measurable disease.
• Written informed consent.

Exclusion criteria:

• Age < 18 years.
• Prior treatment for multiple myeloma.
• Any other prior or ongoing disease/health conditions incompatible with the study objectives.
• Organ function values not met.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) > 2.
• Hypersensitivity to the study medications.
• Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods.
• Male participants who disagree to follow the study contraceptive counseling.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm; Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone; Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone	Drug: Isatuximab SAR650984; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV); Other Names: Sarclisa; Drug: Bortezomib; Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous; Other Names: Velcade®; Drug: Lenalidomide; Pharmaceutical form: Capsules Route of administration: Oral; Drug: Dexamethasone; Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous
Active Comparator: Bortezomib/Lenalidomide/Dexamethasone = VRd arm; Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone; Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone	Drug: Bortezomib; Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous; Other Names: Velcade®; Drug: Lenalidomide; Pharmaceutical form: Capsules Route of administration: Oral; Drug: Dexamethasone; Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous
Other: Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm; 4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone	Drug: Isatuximab SAR650984; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV); Other Names: Sarclisa; Drug: Lenalidomide; Pharmaceutical form: Capsules Route of administration: Oral; Drug: Dexamethasone; Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Defined as the time from the date of randomization to the date of first documentation of progression disease (PD) as determined by the independent review committee (IRC) or the date of death from any cause, whichever occurs first.	Up to approximately 100 months after the First Participant In (FPI)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from the date of randomization to death from any cause	Up to approximately 110 months after the FPI
Time to progression (TTP)	Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria	Up to approximately 100 months after FPI
Time to first response (TT1R)	Time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed	Up to approximately 100 months after the FPI
Time to best response (TTBR)	Defined as the time from randomization to the date of first occurrence of IRC determined best response (PR or better) that is subsequently confirmed	Up to approximately 100 months after the FPI
PFS on next line of therapy (PFS2)	Defined as the time from randomization to the date of first documentation of disease progression (as assessed by investigator) after initiation of further anti-myeloma treatment, or death from any cause, whichever occurs first	Up to approximately 110 months after the FPI
Adverse Events	Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) including infusion associated reactions (IARs), second primary malignancies, laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination	Up to 30 days after end of treatment (EOT) visit
Assessment of PK parameter: Ctrough	Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough)	Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks)
Immunogenicity	Presence of anti-drug antibodies against isatuximab	Up to approximately 100 months after the FPI
PRO: QLQ-MY20	Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire	Up to approximately 100 months after the FPI
PRO: EQ-5D-5L	Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)	Up to approximately 100 months after the FPI
Complete response rate (CR)	Defined as the proportion of participants with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria.	Up to approximately 100 months after the FPI
Minimal residual disease (MRD) negativity rate for participants with CR	Proportion of participants with CR for whom MRD measurement is negative	Up to approximately 100 months after the FPI
Very good partial response (VGPR) or better rate	Proportion of participants with sCR, CR and VGPR as assessed by the IRC using the International Myeloma Working Group (IMWG) criteria	Up to approximately 100 months after the FPI
Overall response rate (ORR)	Proportion of participants with best overall response (BOR) recorded as sCR, CR, VGPR, or partial response (PR) as assessed by the IRC using the IMWG criteria	Up to approximately 100 months after the FPI assessment
Duration of response (DOR)	Defined as the time from date of first IRC determined response to date of first IRC PD or death, whichever occurs first for participants achieving sCR, CR, VGPR, or PR	Up to approximately 100 months after the FPI
PFS in MRD negative participants	Defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first in MRD negative participants	Up to approximately 100 months after the FPI
Sustained MRD negativity ≥12 months rate	Defined as the proportion of participants with the maintenance of MRD negativity confirmed ≥12 months apart with no MRD positive test in between.	Up to approximately 100 months after the FPI
participants reported outcome (PRO): QLQ-C30	Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)	Up to approximately 100 months after the FPI

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Thoren K, Menad S, Nouadje G, Mace S. Isatuximab-Specific Immunofixation Electrophoresis Assay to Remove Interference in Serum M-Protein Measurement in Patients with Multiple Myeloma. J Appl Lab Med. 2024 Jul 1;9(4):661-671. doi: 10.1093/jalm/jfae028.
• Orlowski RZ, Dimopoulos MA, Leleu X, Facon T, Ishida T, Hajek R, Spicka I, Romejko-Jarosinska J, Vorobyev VI, Besemer B, Kalayoglu Besisik S, Robak P, Jelinek T, Goldschmidt H, Martin T, Mohty M, Mace S, Kodas E, Tekle C, Shafer AT, Moreau P. Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study. Blood. 2026 Feb 27:blood.2025030120. doi: 10.1182/blood.2025030120. Online ahead of print.
• Manier S, Dimopoulos MA, Leleu XP, Moreau P, Cavo M, Goldschmidt H, Orlowski RZ, Tron M, Tekle C, Bregeault MF, Shafer AT, Beksac M, Facon T. Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial. Haematologica. 2025 Sep 1;110(9):2139-2150. doi: 10.3324/haematol.2024.287200. Epub 2025 Mar 20.
• Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hajek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Bregeault MF, Mace S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Oct 31;391(17):1597-1609. doi: 10.1056/NEJMoa2400712. Epub 2024 Jun 3.

Helpful Links

• EFC12522 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Estimated): April 5, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Anti-CD38 monoclonal antibody
• 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; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; Dexamethasone; isatuximab
• Other Study ID Numbers: EFC12522; 2017-002238-21 (EudraCT Number); U1111-1194-2121 (Registry Identifier: ICTRP); 2024-514417-34 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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