Clinical Trial Finder

Inclusion Criteria:

• - Participant must be 18 years of age inclusive or older.

• - Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• - Participants with relapsed or refractory MM who have received at least 3 prior lines of therapy for MM, including PIs and IMiDs or at least 2 prior lines if at least one of these lines consisted of 2 or more multiagent regimens (eg, Induction regimen with autologous stem cell transplant followed by maintenance).

• - RRMM with measurable disease: - 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 (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio <0.26 or >1.65).

• - Men or woman or childbearing potential should agree to use contraception.

• - Substudy 01, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 6 months after the last dose.

"Exposure" is defined as at least 2 cycles of therapy.

• - Substudies 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose.

"Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy.

• - Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy prior exposed participants with RRMM.

• - Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy.

For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory.

Exclusion Criteria:

• - Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.

• - Uncontrolled infection within 14 days prior to first study intervention administration.

• - Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration.

, eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction <40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).

• - Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.

• - Uncontrolled or active hepatitis B virus (HBV) infection.

• - Active hepatitis C virus (HCV) infection.

• - Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.

• - Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration.

• - Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone.

• - Participants with a contraindication to treatment.

• - Vaccination with a live vaccine 4 weeks before the start of the study.

• - Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.

• - Hemoglobin <8 g/dL.

• - Platelets <50 × 10^9/L.

• - Absolute neutrophil count <1.5 × 10^9/L.

• - Creatinine clearance <30 mL/min/1.73m2.

• - Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN.

• - Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN.

• - Patients with grade 3 or 4 hypercalcemia.

Substudy 01: -Malabsorption syndrome or any condition that can significantly impact the absorption of pomalidomide. Substudy 02:

• - History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix, or other local tumors, even if considered cured by local treatment.

• - Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the first dose of SAR439459.

• - Prothrombin time or INR >1.5 × upper limit of normal (ULN).

Substudy 03:

• - Current corneal epithelial disease except mild punctate keratopathy.

• - Patients who have received prior therapy with belantamab mafodotin.

Substudy 04:

• - Central nervous system or leptomeningeal disease.

• - Medical history of seizure.

• - Participants currently receiving hepatically metabolized narrow therapeutic index drugs (eg, digoxin, warfarin) if cannot be closely monitored.

Substudy 05:

• - Participant unable to swallow tablets.

Substudy 06:

• - History of active autoimmune disorders.

• - History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.

• - Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD.

• - Prior allogenic hematopoietic stem cell transplant (allo-HSCT) - Hemoglobin < 9g/dL.

• - Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent.

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

Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, Investigator decision, or study termination by the Sponsor i.e., up to Aapproximately 28 months.

Arms

Active Comparator: Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01)

Isatuximab, intravenous (IV) doseweekly (QW) × 4 weeks (Cycle 1), followed by every two weeks (Q2W) (subsequent cycles). Pomalidomide dose by mouth daily Day 1 to Day 21. Dexamethasone dose by mouth QW.

Experimental: isatuximab + SAR439459 + dexamethasone (Substudy 02)

SAR439459 in combination with isatuximab and dexamethasone Part 1: 2 dose levels (DLs) of IV SAR439459: DL1 SAR439459 dose Q2W. DL2 SAR439459 dose Q2W. Isatuximab dose IV QW × 5 weeks (Cycle 1), followed by Q2W administrations (subsequent cycles). Dexamethasone fixed dose and schedule: QW by mouth In Cycle 1, the first administration of SAR439459 (Day 1) will precede isatuximab by 1 week (first dose of isatuximab will be at Cycle 1 Day 8). Part 2: SAR439459 IV dose Q2W. Isatuximab IV dose QW × 5 weeks (Cycle 1), followed by Q2W administrations (subsequent cycles). Dexamethasone fixed dose and schedule: QW by mouth. In Cycle 1, the first administration of SAR439459 (Day 1) will precede isatuximab by 1 week (first dose of isatuximab will be at Cycle 1 Day 8).

Experimental: isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)

Belantamab mafodotin in combination with isatuximab and dexamethasone Part 1: 1 DL of IV belantamab mafodotin in Part 1 and de-escalation dose DL-1: DL1 belantamab mafodotin IV dose QW4 or de-escalation dose DL-1 QW8 Isatuximab dose, IV QW × 4 weeks (Cycle 1), followed by Q2W (subsequent cycles). Dexamethasone fixed dose and schedule: QW by mouth. Part 2: Isatuximab IV dose QW × 4 weeks (Cycle 1), followed by Q2W (subsequent cycles). Belantamab mafodotin IV dose Q4W or Q8W Dexamethasone fixed dose and schedule: QW by mouth.

Experimental: Isatuximab + pegenzileukin (Substudy 04)

Pegenzileukin in combination with isatuximab Part 1- dose escalation: Up to 3 DLs of IV pegenzileukin are planned to be evaluated: DL1 will explore pegenzileukin at Q2W. DL2 will explore pegenzileukin at Q2W. DL3 will explore pegenzileukin at Q2W. Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles). Part 1 - dose optimization: Isatuximab IV doseQW × 4 weeks, followed by Q2W (subsequent cycles). Pegenzileukin at potential doses (DL A and DL B) Q2W. Part 2 (dose expansion): Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles). Pegenzileukin IV dose Q2W.

Experimental: Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)

Isatuximab in combination with belumosudil and dexamethasone Part 1- dose escalation: During the first cycle, belumosudil will be evaluated in monotherapy during 2 to 4 weeks, then isatuximab and dexamethasone will be added, and continued for the subsequent cycles. Belumosudil by mouth at Dose Level (DL) 1, DL2, DL3, and DL4 Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth Part 1- dose optimization: Belumosudil at potential doses (DL A and DL B), daily by mouth Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth Part 2- dose expansion: Belumosudil dose daily, by mouth Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth

Experimental: Isatuximab + evorpacept + dexamethasone (Substudy 06)

Isatuximab in combination with evorpacept and dexamethasone Part 1- dose escalation: Evorpacept IV dose Q2W Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth Part 1- dose optimization Evorpacept IV at potential doses (DL A and DL B), Q2W Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth Part 2- dose expansion: Evorpacept IV dose Q2W Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles) Dexamethasone fixed dose and schedule: QW by mouth

Interventions

Drug: - Isatuximab

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Drug: - Dexamethasone

Pharmaceutical form: Tablet; Route of administration: Oral

Drug: - Pomalidomide

Pharmaceutical form: Capsule; Route of administration: Oral

Drug: - Belantamab mafodotin

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Drug: - Pegenzileukin

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Drug: - SAR439459

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Drug: - Belumosudil

Pharmaceutical form: tablet; route of administration: oral

Drug: - Evorpacept

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous