This phase I/II trial has been designed to find the recommended dose of a targeted therapy drug and determine whether it is more effective than chemotherapy as treatment for multiple myelomaPhase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol

Exclusion

• 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.