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

A Single-arm, Open-label, Phase 2 Study Evaluating Subcutaneous Administration of Isatuximab, Administered by an On Body Delivery System, in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)

The primary purpose of this study is to assess the efficacy (overall response rate) of subcutaneous (SC) via on body delivery system (SC-OBDS) isatuximab in combination with weekly carfilzomib and dexamethasone (Kd) in adult participants with RRMM having received 1 to 3 prior lines of therapy.

Study Overview

• Status: Recruiting
• Conditions: Plasma Cell Myeloma Refractory
• Intervention / Treatment: Drug: Isatuximab SC-OBDS; Drug: Montelukast; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone; Drug: Carfilzomib

Detailed Description

The duration of the study for a participant will include a period for screening of up to 28 days, a study treatment period of 12 months (except early discontinuation), the end-of-treatment (EOT) visit about 30 days after the last dose of study treatment, and a study follow-up period until death or the final study cut-off date. A cycle duration is 28 days. After study treatment discontinuation, participants will return to the study site 30 days after the last dose of study treatment for the EOT visit or before further anti-myeloma therapy initiation, whichever comes first.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic in Arizona - Phoenix- Site Number : 8400058
  • California
    • Los Angeles, California, United States, 90017
      • Recruiting
      • Los Angeles Hematology Oncology Medical Group- Site Number : 8400027
    • West Hollywood, California, United States, 90069
      • Recruiting
      • Private Practice - Dr. James R. Berenson- Site Number : 8400044
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Smilow Cancer Center at Yale-New Haven- Site Number : 8400020
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20017
      • Recruiting
      • Maryland Oncology Hematology- Site Number : 8400038
  • Florida
    • Coral Springs, Florida, United States, 33071
      • Recruiting
      • Life Clinical Trials - Coral Springs- Site Number : 8400055
    • Fort Lauderdale, Florida, United States, 33309
      • Recruiting
      • Center for Rheumatology, Immunology and Arthritis- Site Number : 8400031
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida- Site Number : 8400002
    • Lakeland, Florida, United States, 33812
      • Recruiting
      • The Oncology Institute of Hope & Innovation - Lakeland- Site Number : 8400054
    • Margate, Florida, United States, 33063
      • Recruiting
      • D&H Pompano Research Center- Site Number : 8400049
    • Pembroke Pines, Florida, United States, 33024
      • Recruiting
      • Millennium Oncology - Pembroke Pines- Site Number : 8400011
    • Plantation, Florida, United States, 33322
      • Recruiting
      • BRCR Global- Site Number : 8400008
    • St. Petersburg, Florida, United States, 33705
      • Recruiting
      • Florida Cancer Specialists - North- Site Number : 8400030
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Recruiting
      • Pontchartrain Cancer Center - Covington- Site Number : 8400046
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center - Boston- Site Number : 8400005
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • Recruiting
      • Michigan Hematology & Oncology Consultants - Dearborn- Site Number : 8400036
    • Royal Oak, Michigan, United States, 48073
      • Recruiting
      • Hematology Oncology Consultants - Royal Oak- Site Number : 8400039
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Recruiting
      • Alliance for Multispeciality Research - Kansas City- Site Number : 8400056
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University- Site Number : 8400007
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400021
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • Recruiting
      • San Juan Oncology Associates- Site Number : 8400016
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center - New York - York Avenue- Site Number : 8400003
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center- Site Number : 8400018
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center- Site Number : 8400010
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center- Site Number : 8400043
    • Cincinnati, Ohio, United States, 45236
      • Recruiting
      • Oncology Hematology Care - Kenwood- Site Number : 8400014
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Recruiting
      • Roper Saint Francis Healthcare- Site Number : 8400013
    • Greenville, South Carolina, United States, 29615
      • Recruiting
      • Prisma Health Cancer Institute - Greenville- Site Number : 8400019
    • Spartanburg, South Carolina, United States, 29303
      • Recruiting
      • Gibbs Cancer Center & Research Institute - Spartanburg- Site Number : 8400001
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center- Site Number : 8400006
    • Knoxville, Tennessee, United States, 37909
      • Recruiting
      • Tennessee Cancer Specialists - Knoxville - Old Weisgarber Road- Site Number : 8400035
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology Nashville- Site Number : 8400012
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Northern Virginia Oncology Group- Site Number : 8400045
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Recruiting
      • SSM Health Dean Medical Group - Wisconsin - Madison- Site Number : 8400009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a documented diagnosis of 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).
• Participants with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.

• Contraceptive use by [men and women] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  • Male participants agree to practice true abstinence or agree to use contraception while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP XE " FCBP " \f Abbreviation \t "female of childbearing potential" ) or agrees to practice complete abstinence or use contraception.
• Capable of giving signed informed consent.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• 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 < 6 months before first isatuximab administration or, b) intolerant to the anti-CD38 previously received.
• Participants who are refractory to 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.
• Participants with contraindication to dexamethasone and/or to carfilzomib.
• Any anti-myeloma drug treatment within 14 days before the first isatuximab administration, including dexamethasone.
• Prior allogenic HSC transplant with active graft versus host disease (GvHD XE " GvHD " \f Abbreviation \t "graft versus host disease" ) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months).
• Any major procedure within 14 days before the first isatuximab administration: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy.
• Vaccination with a live vaccine within 4 weeks before the first isatuximab administration. Seasonal flu vaccines that do not contain live virus are permitted.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Isatuximab in combination with weekly carfilzomib and dexamethasone; Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.

Drug: Isatuximab SC-OBDS; Pharmaceutical form:Solution for SC-OBDS administration-Route of administration:SC-OBDS; Other Names: SAR650984; Sarclisa; Drug: Montelukast; Pharmaceutical form:As per local commercial product-Route of administration:Oral; Drug: Dexamethasone; Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV; Drug: Acetaminophen; Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV; Drug: Diphenhydramine; Pharmaceutical form:As per local commercial product-Route of administration:Oral (as premedication) or IV/oral equivalent (for management of infusion reaction); Drug: Methylprednisolone; Pharmaceutical form:As per local commercial product-Route of administration:IV; Drug: Carfilzomib; Pharmaceutical form:As per local commercial product-Route of administration:IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	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 IMWG criteria assessed by investigator.	6 months after the Last Participant In (LPI) i.e., approximately 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with infusion reactions (IRs)		From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities (per NCI-CTCAE grade or PCSA if NCI-CTCAE scale is not applicable)		From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months
Number of participants with injection site reactions (ISRs)		From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months
CR or better	CR or better assessed according to International Myeloma Working Group (IMWG) criteria assessed by investigator. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow aspirates, and a normal FLC ratio of 0.26-1.65 is required for FLC disease only. Two consecutive assessments are needed. No known evidence of progressive disease or new bone/soft tissue lesions if radiographic studies were performed.	12 months after the Last Participant In (LPI) i.e., approximately 38 months
VGPR or better	VGPR or better assessed according to IMWG criteria assessed by investigator. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h, or ≥90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. FLC only: a ≥90% decrease in the difference between involved and uninvolved FLC levels. Two consecutive assessments are needed. No known evidence of progressive disease or new bone/soft tissue lesions if radiographic studies were performed.	12 months after the Last Participant In (LPI) i.e., approximately 38 months
Duration of response (DOR)	DOR, defined as the time from date of first investigator determined response for achieving PR or better to first documentation of progressive disease (PD) determined by investigator or death, whichever occurred first.	12 months after the Last Participant In (LPI) i.e., approximately 38 months
Time to first response (TT1R)	TT1R, defined as the time from first isatuximab administration to first investigator-determined response (PR or better) that is subsequently confirmed.	12 months after the Last Participant In (LPI) i.e., approximately 38 months
Time to best response (TTBR)	TTBR, defined as the time from first isatuximab administration to first occurrence of investigator-determined best response (PR or better) that is subsequently confirmed.	12 months after the Last Participant In (LPI) i.e., approximately 38 months
Patient experience and Satisfaction Questionnaire v2 (PESQ v2)	The PESQ v2 has been designed to follow up on participant experience and satisfaction regarding the treatment (side effects and recommendation) and the administration method (comfortability, pain, side effects and overall satisfaction). This questionnaire has been developed using industry standard for instrument development and has been debriefed and adapted based on qualitative interviews with oncology patients. The more general treatment expectations instrument (v1) was further adapted and debriefed with patients to assess manual and OBDS subcutaneous delivery (v2). The trial specific version of the PESQ v2 contains of items administered for the duration of treatment. Response options are presented as a 5-point Likert scale ranging from Strongly agree/very satisfied/definitely yes to strongly disagree/very dissatisfied/definitely no.	Cycle 3/Day 15 and Cycle 6/Day 15
Positivity titer of anti-drug antibodies (ADA) in a subset of approximately 30 participants	Blood samples will be collected for assessing the presence of ADA against isatuximab in plasma from approximately 30 participants. Plasma samples will be screened for antibodies binding to isatuximab and the titer of confirmed positive samples will be reported.	From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e, approximately up to 15 months (1 cycle = 28 days)
Maximum observed concentration (Cmax) of isatuximab in a subset of approximately 30 participants		Multiple timepoints in Cycle 1 (1 cycle = 28 days)
Cumulative area under the curve over the first 4 weeks of isatuximab treatment (AUC4 weeks) in a subset of approximately 30 participants		Multiple timepoints in Cycle 1 (1 cycle = 28 days)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• LPS18183 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2025
• Primary Completion (Estimated): January 8, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: April 5, 2024
• First Submitted That Met QC Criteria: April 5, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Anti CD38 monoclonal antibody; SARCLISA
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Pregnadienetriols; Ethylamines; Prednisolone; Benzhydryl Compounds; Dexamethasone; Acetaminophen; Methylprednisolone; Diphenhydramine; carfilzomib; isatuximab; montelukast
• Other Study ID Numbers: LPS18183; U1111-1298-7348 (Other Identifier: WHO ICTRP)

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