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 2 prior lines
of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous
stem cell transplant followed by maintenance is considered one line).

- 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 12 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 (if
available) prior exposed participants with RRMM. For anti-CD38, "Exposure" is
defined as at least 2 cycles of therapy. For anti-BCMA therapy if available,
exposure is defined by at least 2 cycles of therapy.

- 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 <1.0 × 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.

- Active, known, or suspected autoimmune disease that has required systemic treatment
in the past 2 years (ie, with use of disease modifying agents, corticosteroids or
immunosuppressive drugs), except controlled by replacement therapy (eg, thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc). The following are not exclusionary: vitiligo, childhood asthma
that has resolved, psoriasis that does not require systemic treatment.

- Prior allogeneic hematopoietic stem cell transplant (allo-HSCT).

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).

- Patient with chronic active EBV infection.

- Patients with known history of HLH.

- Hemoglobin < 9 g/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.