Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies

The Phase 1 study duration for an individual patient will include a screening period for
inclusion of up to 2 weeks, treatment with Isatuximab QW (every week) or Q2W (every 2 weeks)
unless discontinued earlier due to safety or disease progression. Patients will be followed
for a minimum of 30 days following the last use of study drug or more than 30 days in case of
unresolved toxicity, or up to initiation of another anticancer treatment.

The Phase 2 study duration for an individual patient will include a screening period for
inclusion of up to 3 weeks, then a treatment period and a follow up period. Treatment will
continue until disease progression, unacceptable adverse reactions or other reasons for
discontinuation. Patients will be followed every 3 months following the last use of study
drug until death or study cutoff whichever comes first.

Inclusion criteria:

Phase 1:

- For dose escalation cohorts, patients with confirmed selected CD38+ hematological
malignancies as specified below who have progressed on after standard therapy or for
whom there is no effective standard therapy (refractory/relapsed patients). B-cell
Non-Hodgkin-lymphoma/leukemia (NHL) patients having at least 1 measurable lesion.
Multiple myeloma (MM) patients with measurable M-protein serum and/or 24-hour urine.
Acute myeloid leukemia (AML) patients, all types except M3 based on
French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell
ALL) patients. Chronic lymphocytic leukemia (CLL) patients.

- For expansion cohorts, patients with relapsed/refractory MM with measurable M-protein
(serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg (24-hr urine)) or
elevated serum free light chains (FLC) >10 mg/dL with abnormal FLC ratio) who have
progressed on or after standard therapy that includes an iMiD and a proteasome
inhibitor and who meet the protocol defined criteria for standard risk or high risk.

Phase 2:

- Patients must have a known diagnosis of multiple myeloma with evidence of measurable
disease, and have evidence of disease progression based on International Myeloma
Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein ≥200 mg/24
hours or in the absence of measurable m-protein, serum FLC ≥10 mg/dL, and abnormal
serum immunoglobulin kappa lambda FLC ratio (<0.26 or >1.65).

- Patients must have received at least three prior lines of therapy for MM and must
include treatment with an Immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of
treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment)
OR patients whose disease is double refractory to an IMiD and a PI. For patients who
have received more than 1 type of IMiD and PI, their disease must be refractory to the
most recent one.

- Patients must have achieved a minimal response or better to at least one prior line of
therapy.

- Patients must have received an alkylating agent (≥2 cycles or ≥2 months) either alone
or in combination with other MM treatments.

- Stage 2 only: Patients must have evidence of disease progression on or after the most
recent prior regimen based on IMWG criteria.

Exclusion criteria:

Phase 1:

- Karnofsky performance status <60

- Poor bone marrow reserve

- Poor organ function

- Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or
known hypersensitivity to any of the components of the study therapy that is not
amenable to pre-medication with steroids and H2 blockers

- Any serious active disease (including clinically significant infection that is
chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the
investigator, could interfere with the safety, the compliance with the study or with
the interpretation of the results

- Any severe underlying medical conditions including presence of laboratory
abnormalities, which could impair the ability to participate in the study or the
interpretation of its results

Phase 2:

- Patients with multiple myeloma immunoglobulin M (IgM) subtype

- Previous treatment with any anti-CD38 therapy

- Patients with concurrent plasma cell leukemia

- Patients with known or suspected amyloidosis

- Karnofsky performance status <60 (stage 1)/ECOG Performance status >2 (stage 2).

- Poor bone marrow reserve

- Poor organ function

- Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or
known hypersensitivity to any of the components of the study therapy that is not
amenable to pre-medication with steroids and H2 blockers

- Any serious active disease (including clinically significant infection that is
chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the
investigator, could interfere with the safety, the compliance with the study or with
the interpretation of the results

- Any severe underlying medical conditions including presence of laboratory
abnormalities, which could impair the ability to participate in the study or the
interpretation of its results

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