Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

Primary Objectives:

• To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV)
• To assess the safety and tolerability (including local injection site tolerability) of isatuximab using the (investigational) isatuximab injector device
• To evaluate the pharmacokinetics (PK) of SC and IV isatuximab

Secondary Objectives:

• To estimate absolute bioavailability of SC and IV isatuximab
• To measure receptor occupancy (RO) after isatuximab SC versus IV administration
• To assess efficacy of isatuximab after SC and IV administration
• To assess patient expectations prior to and patient experience and satisfaction after SC administration
• To evaluate potential immunogenicity of SC or IV isatuximab

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: pomalidomide; Drug: dexamethasone; Drug: isatuximab SAR650984 SC; Device: Investigational injector device; Drug: isatuximab SAR650984 IV

Detailed Description

Total study duration is variable depending on treatment and follow-up periods, including 21 days of screening, and treatment period until disease progression, unacceptable adverse reaction or other reason for discontinuation. End of treatment will be 30 days after last administration of investigational medicinal product, or before further anti-myeloma therapy, whichever comes first; approximately 14 months after first study treatment administration.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Investigational Site Number : 0360002
    • Wollongong, New South Wales, Australia, 2500
      • Investigational Site Number : 0360001
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Investigational Site Number : 0360004
    • Richmond, Victoria, Australia, 3121
      • Investigational Site Number : 0360003
• Belgium
  • Leuven, Belgium, 3000
    • Investigational Site Number : 0560001
• France
  • Nantes, France, 44093
    • Investigational Site Number : 2500001
  • Toulouse, France, 31059
    • Investigational Site Number : 2500002
• Japan
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 701-1192
      • Investigational Site Number : 3920002
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Investigational Site Number : 3920001
• Spain
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Investigational Site Number : 7240002
  • Catalunya [Cataluña]
    • Badalona, Catalunya [Cataluña], Spain, 08916
      • Investigational Site Number : 7240001
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • ~Banner MD Anderson Cancer Center Site Number : 8400005
  • California
    • Duarte, California, United States, 91010
      • City of Hope Site Number : 8400002
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Site Number : 8400001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Participant must be above 18 years of age or country's legal age of majority if the legal age is >18 years old, at the time of signing the informed consent.
• Participant has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
• Participant has received at least two previous therapies including lenalidomide and a proteasome inhibitor and has demonstrated disease progression on last therapy or after completion of the last therapy.
• Participants with measurable disease defined as at least one of the following:
• Serum M protein ≥ 0.5 g/dL (≥5 g/L).
• Urine M protein ≥ 200 mg/24 hours.
• 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).
• Male or female: Contraceptive use by men or women

Exclusion criteria:

• Malignancy within 3 years prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score >2.
• Inadequate hematological, liver or renal function.
• Serum calcium (corrected for albumin) level above the upper limit of normal (ULN) range.

• Patients with prior anti-CD38 treatment are excluded if:

  • Refractory to anti-CD38 treatment defined as progression on or within 60 days of the last dose of the anti-CD38 or,
  • Intolerant to the anti-CD38 previously received or,
  • Progression after initial response on anti-CD38 therapy with a washout period inferior to 9 months before the first dose of isatuximab SC or IV.
• Participant did not achieve a minimal response or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible).
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
• Prior anti-cancer therapy within 14 days.
• Any >Grade 1 adverse reaction unresolved from previous treatments according to the NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed.
• Previous allogeneic stem cell transplantation with active Graft Versus Host Disease or being under immunosuppressive therapy in the last 2 months previously to the inclusion in the trial.
• Daily requirement for corticosteroids.
• Known to be HIV+ or to have hepatitis A or uncontrolled or active hepatitis B virus (HBV) infection (patients with positive HBsAg [HBsAg] and/or HBV DNA) or active HCV (HCV) infection (positive HCV RNA and negative anti-HCV).
• Active tuberculosis and severe infections requiring treatment with antibiotic parenteral administration.
• Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
• History of erythema multiforme or severe hypersensitivity to prior immunomodulatory drugs (IMiDs).
• Hypersensitivity or history of intolerance to immunomodulatory drugs (IMiDs), dexamethasone, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and histamine H2 blockers or would prohibit further treatment with these agents.
• Inability to tolerate thromboprophylaxis.

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: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose regimen 1; Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle	Drug: pomalidomide; Pharmaceutical form: tablet Route of administration: oral; Other Names: Pomalyst®; Drug: dexamethasone; Pharmaceutical form: tablet Route of administration: oral; Other Names: Decadron®; Drug: isatuximab SAR650984 SC; Pharmaceutical form: solution Route of administration: subcutaneous
Experimental: Dose regimen 2; Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle	Drug: pomalidomide; Pharmaceutical form: tablet Route of administration: oral; Other Names: Pomalyst®; Drug: dexamethasone; Pharmaceutical form: tablet Route of administration: oral; Other Names: Decadron®; Drug: isatuximab SAR650984 SC; Pharmaceutical form: solution Route of administration: subcutaneous
Experimental: Dose regimen 3; Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle	Drug: pomalidomide; Pharmaceutical form: tablet Route of administration: oral; Other Names: Pomalyst®; Drug: dexamethasone; Pharmaceutical form: tablet Route of administration: oral; Other Names: Decadron®; Drug: isatuximab SAR650984 SC; Pharmaceutical form: solution Route of administration: subcutaneous; Device: Investigational injector device; Subcutaneous administration
Experimental: Dose regimen 4; Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle	Drug: pomalidomide; Pharmaceutical form: tablet Route of administration: oral; Other Names: Pomalyst®; Drug: dexamethasone; Pharmaceutical form: tablet Route of administration: oral; Other Names: Decadron®; Drug: isatuximab SAR650984 IV; Pharmaceutical form: solution Route of administration: intravenous; Other Names: Sarclisa
Experimental: Dose regimen 5; Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle	Drug: pomalidomide; Pharmaceutical form: tablet Route of administration: oral; Other Names: Pomalyst®; Drug: dexamethasone; Pharmaceutical form: tablet Route of administration: oral; Other Names: Decadron®; Drug: isatuximab SAR650984 IV; Pharmaceutical form: solution Route of administration: intravenous; Other Names: Sarclisa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of adverse events (AEs)	Number of participants with adverse events	Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
Pharmacokinetic (PK) assessment: Ceoi	Concentration observed at the end of infusion (Ceoi)	Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Cmax	Maximum concentration observed after the first infusion (Cmax)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: tmax	Time to reach Cmax (tmax)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Clast	Last concentration observed above the lower limit of quantification after the first infusion (Clast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: tlast	Time of Clast (tlast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Ctrough	Concentration observed just before treatment administration during repeated dosing (Ctrough)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: AUClast	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: AUC0 T	Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimation of absolute bioavailability of isatuximab	Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration	Day 8
Overall response rate (ORR)	ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Duration of response (DOR)	Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Time to response (TTR)	Time from the date of first study treatment to the first response	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Time to progression (TTP)	Time from date of first study treatment to date of first documentation of progressive disease	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Overall survival (OS)	Time from the date of first study treatment to date of death from any cause	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Clinical benefit rate (CBR)	Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Progression free survival (PFS)	Time from date of first study treatment to date of first documentation of progressive disease or death	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires	Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied	Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration)
Immunogenicity: Anti drug antibody levels	Incidence of patients with anti drug antibodies against isatuximab	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Biomarker: Change in CD38 receptor occupancy	Change in CD38 receptor occupancy from baseline	At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• TCD15484 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2019
• Primary Completion (Actual): March 27, 2024
• Study Completion (Actual): March 27, 2024

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

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; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Pregnadienetriols; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Dexamethasone; Calcium Dobesilate; pomalidomide; isatuximab
• Other Study ID Numbers: TCD15484; 2018-001996-19 (EudraCT Number); U1111-1211-9525 (Registry Identifier: 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: Yes
• product manufactured in and exported from the U.S.: Yes