To determine the maximum tolerated dose (MTD) of SAR442257 administered as a single agent in
patients with relapsed and refractory multiple myeloma (RRMM) and refractory non-Hodgkin
lymphoma (RR-NHL), and determine the recommended Phase 2 dose (RP2D)
To characterize the safety profile of SAR442257 To characterize the pharmacokinetics (PK)
profile of SAR442257 To evaluate the potential immunogenicity of SAR442257 To assess
preliminary evidence of antitumor activity
Inclusion criteria :
Participant must be at least 18 years of age or of the country's legal age of majority if
the legal age is >18 years old, at the time of signing the informed consent.
Life expectancy of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance
must have received at least 3 prior lines of therapy including proteasome inhibitor (PI),
immunomodulatory agent (IMiD), and anti-CD38 mAb; and must have received their last dose of
prior anti-CD38 therapy within 9 months prior to the first dose of SAR442257; and must be
refractory to anti-CD38 antibody (eg, daratumumab or isatuximab), characterized by
progression within 60 days of the last dose of anti-CD38, regardless of which line it was
given; and must be either relapsed or refractory to all established therapies with known
clinical benefit in RRMM where approved and available, or are intolerant to those
established therapies; and must not be candidates for regimens known to provide clinical
Patients with RRMM must have measurable disease as per the following:
- Serum M protein ≥0.5 g/dL (≥5 g/L), or
- Urine M protein ≥200 mg/24 hours, or
- Serum free light chain (FLC) assay: involved FLC assay ≥10 mg/dL and an abnormal serum
FLC ratio (<0.26 or >1.65).
Patients with RR-NHL must be relapsed or refractory to all established therapies with known
clinical benefit where approved and available, or are intolerant to those established
Patients with RR-NHL must have measurable disease of at least one lesion ≥1.5 cm as
documented by computed tomography (CT) scan, including the following subtype of disease:
- Diffuse large B-cell lymphoma (DLBCL).
- transformed follicular lymphoma (tFL),
- follicular lymphoma (FL),
- mantle cell lymphoma (MCL),
- marginal zone lymphoma (MZL),
- lymphoplasmacytic lymphoma,
- small lymphocytic lymphoma (SLL). Patients with RR-NHL subtype T cell lymphoma (TCL):
histopathologically confirmed mycosis fungoides or Sézary syndrome (cutaneous T cell
lymphoma [CTCL] stage IIB or greater according to the European Organization for
Research and Treatment of Cancer/International Society for Cutaneous Lymphomas
[EORTC-ISCL] consensus classification) at study entry with progressive, persistent, or
recurrent disease who have no available remaining standard therapeutic options (ie,
refractory) as determined by the Investigator.
Patients with lymphoma must have availability of lymphoma tissue for biomarker testing:
either archived tissue or a fresh biopsy as a part of screening. On-treatment biopsy (Cycle
2 or beyond) is also expected if disease location is in a superficial lymph node.
Excisional biopsy or resected tissue is required if clinically feasible; otherwise, core
needle biopsy is acceptable. Fine needle aspirates are not acceptable.
Patients with lymphoma must have a ≥50% left ventricular ejection fraction (LVEF) and no
pericardial effusion, as measured by echocardiogram (ECHO).
Contraceptive use by men or women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
Diagnosed or treated for another malignancy within 3 years prior to enrollment, except for
basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy,
superficial bladder carcinoma or low risk prostate cancer.
Amyloidosis, leukemic manifestations of lymphoma, chronic lymphocytic leukemia and
Richter's transformation, and prolymphocytic leukemia.
Known central nervous system (CNS) involvement by myeloma, lymphoma or other CNS disease
such as neurodegenerative condition or CNS movement disorder.
Has congestive heart failure (New York Heart Association) Grade ≥II; cardiomyopathy, active
ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically
significant arrhythmia requiring therapy including anticoagulants, or clinically
significant uncontrolled hypertension, QT interval corrected by the Fridericia method >480
msec (Grade ≥2). Acute myocardial infarction within 6 months before start of study
Has active autoimmune disease including autoimmune hemolytic anemia, idiopathic
thrombocytopenic purpura, inflammatory bowel syndrome, pneumonitis or any chronic condition
requiring a higher corticosteroid systemic equivalent than prednisone 10 mg daily.
Clinically-not controlled chronic or ongoing infectious disease requiring treatment at the
time of first dose or within the 14 days before first dose.
Active hepatitis A, B, and C as defined below: active hepatitis A (defined as positive
IgM), active hepatitis B (defined as either positive hepatitis B surface antigen or
positive hepatitis B viral DNA test above the lower limit of detection of the assay, and
hepatitis B core antibodies), or C infection (defined as a known positive hepatitis C
antibody result and known quantitative hepatitis C [HCV] ribonucleic acid [RNA] results
greater than the lower limits of detection of the assay).
Known positivity for Human Immunodeficiency Virus (HIV). Unresolved toxicities from prior
anticancer therapy, defined as not having resolved to Common Terminology Criteria for
Adverse Events (CTCAE) version 5.0 Grade 1 or to levels dictated in the eligibility
criteria with the exception of Grade 1 peripheral neuropathy, alopecia or toxicities from
prior anticancer therapy that are considered irreversible (defined as having been present
and stable for >4 weeks) which may be allowed if they are not otherwise described in the
Participant not suitable for participation, whatever the reason, as judged by the
Investigator, including medical or clinical conditions, or participants potentially at risk
of noncompliance to study procedures.
Sensitivity to any of the study interventions, or components thereof, or drug or other
allergy that, in the opinion of the Investigator, contraindicates participation in the
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.