Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

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.