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

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.

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.

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