A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma

NCT05704049 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: ACT17453U1111-1280-50902023-508870-27
• Study Type: interventional
• Target: 118
• Locations: 7 countries
• Sites: 23

Brief Summary

The main purpose of this study is to measure the efficacy (Myeloma response) of subcutaneous (SC) isatuximab treatment in combination with carfilzomib and dexamethasone in adult participants with RRMM having received 1 to 3 prior lines of therapy, and to characterize the PK of isatuximab in combination with carfilzomib and dexamethasone after manual and On Body Delivery System (OBDS) administration. After confirmation of the feasibility of SC isatuximab by manual administration, patient will be randomized to 1 of the 2 delivery methods of SC isatuximab.

Conditions

Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Overall response rate (ORR) - Cohorts 1 to 3

  ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).

  6 months after the Last Participant In (LPI) i.e., approximately 16 months

• Maximum observed concentration (Cmax) over Cycle 1- Cohorts 4 to 5

  Cycle 1 (28 days)

• Cumulative area under the curve over the first 4 weeks (AUC4weeks) of isatuximab treatment- Cohorts 4 to 5

  Cycle 1 (28 days)

Secondary Outcomes (17)

• Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6

  6 months from LPI i.e., approximately 16 months

• Incidence rate of infusion reactions (IRs)

  From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months

• Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters

  From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months

• Incidence rate of injection site reactions (ISRs)

  18 months after LPI i.e., approximately 28 months

• PK concentration: trough plasma concentration (Ctrough)

  Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)

Study Arms (8)

Cohort 1: manual administration

EXPERIMENTAL

Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 1 Cohort 2: manual administration

EXPERIMENTAL

Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 2 Cohort 3 Randomized Cohort: OBDS to manual

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 2 Cohort 3 Randomized Cohort: Manual to OBDS

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 3 Cohort 4 Randomized Cohort: OBDS to manual

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 3 Cohort 4: Randomized Cohort: manual to OBDS

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

EXPERIMENTAL

Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.

Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Interventions

Isatuximab DRUG

Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Carfilzomib DRUG

Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous

Also known as: Kyprolis

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Dexamethasone DRUG

Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Dexamethasone IV DRUG

Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Montelukast DRUG

Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Acetaminophen DRUG

Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV)

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Diphenhydramine DRUG

Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Methylprednisolone DRUG

Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV

Cohort 1: manual administration; Part 1 Cohort 2: manual administration; Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a documented diagnosis of multiple myeloma (MM)
• Participants with measurable disease defined as at least one of the following:
• Serum M-protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
• Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
• Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
• Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP) or agrees to practice complete abstinence or use approved contraception methods.
• Male participants agree to practice true abstinence or agree to use approved contraception methods while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
• Capable of giving signed informed consent.

You may not qualify if:

• Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course
• Participants with prior anti-CD38 treatment if: a) administered \<9 months before first isatuximab administration or randomization as applicable or, b) Intolerant to the anti-CD38 previously received
• Prior treatment with carfilzomib
• Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents
• Uncontrolled or active infection with hepatitis A, B, and C virus; known acquired immunodeficiency syndrome (AIDS)-related illness; active primary amyloid light chain (AL) amyloidosis
• Any severe acute or chronic medical condition which could impair the ability of the participant to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or participant unable to comply with the study procedures.
• The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (23)

Investigational Site Number : 0360002

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360001

Melbourne, Victoria, 3065, Australia

Location

Hospital Mae de Deus Site Number : 0760002

Porto Alegre, Rio Grande do Sul, 90880-480, Brazil

Location

Clinica São Germano- Site Number : 0760003

São Paulo, 04537-080, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo- Site Number : 0760001

São Paulo, 05403-000, Brazil

Location

Investigational Site Number : 1560006

Changsha, 410013, China

Location

Investigational Site Number : 1560002

Guangzhou, 510060, China

Location

Investigational Site Number : 1560005

Nanchang, 330006, China

Location

Investigational Site Number : 1560004

Shenyang, 110004, China

Location

Investigational Site Number : 1560001

Tianjin, 300020, China

Location

Investigational Site Number : 1560007

Tianjin, 300060, China

Location

Investigational Site Number : 1560003

Wuhan, 430030, China

Location

Investigational Site Number : 2030002

Brno, 625 00, Czechia

Location

Investigational Site Number : 2030004

Olomouc, 779 00, Czechia

Location

Investigational Site Number : 2030003

Ostrava, 708 52, Czechia

Location

Investigational Site Number : 2030001

Prague, 128 08, Czechia

Location

Investigational Site Number : 3000001

Athens, 106 76, Greece

Location

Investigational Site Number : 3000002

Athens, 115 28, Greece

Location

Investigational Site Number : 3920001

Kashiwa, Chiba, 277-8577, Japan

Location

Investigational Site Number : 3920002

Okayama, 701-1192, Japan

Location

Investigational Site Number : 6200001

Braga, 4710-243, Portugal

Location

Investigational Site Number : 6200004

Lisbon, 1400-038, Portugal

Location

Investigational Site Number : 6200005

Lisbon, 1649-035, Portugal

Location

Related Publications (1)

• Parmar G, Capra M, Seguro F, Hungria V, Dimopoulos MA, Delimpasi S, Minarik J, Spicka I, Pour L, Marques H, Esteves G, Sunami K, Yuda J, Hajek R, Mihalyova J, Soufflet C, Yu D, Benlhassan K, Koch V, Comerford E, Cordero P, Suzan F, Quach H. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. Blood Cancer J. 2025 Dec 27;16(1):16. doi: 10.1038/s41408-025-01436-0.

  PMID: 41455697 DERIVED

Related Links

• ACT17453 Plain Language Results Summary

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; carfilzomib; Dexamethasone; montelukast; Acetaminophen; Diphenhydramine; Methylprednisolone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Prednisolone

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 30, 2023
• Study Start: April 5, 2023
• Primary Completion: December 22, 2025
• Study Completion (Estimated): May 12, 2028
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); GR (2); CZ (4); PT (3); BR (3); CN (7); JP (2)