Official Title
An Open-label, First-in-human, Single Agent, Dose Escalation Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR442257 in Patients With Relapsed and Refractory Multiple Myeloma and Relapsed and Refractory Non-Hodgkin Lymphoma
Brief Summary

Primary Objective:To determine the maximum tolerated dose (MTD) of SAR442257 administered as a single agentin patients with relapsed and refractory multiple myeloma (RRMM) and relapsed andrefractory non-Hodgkin lymphoma (RR-NHL), and determine the recommended Phase 2 dose(RP2D)Secondary Objectives: - To characterize the safety profile of SAR442257 - To characterize the pharmacokinetics (PK) profile of SAR442257 - To assess preliminary evidence of antitumor activity

Detailed Description

Study duration per participant is 2 months to estimated 16 months. Cycle lengths in this
study are 27 days in Cycle 1 and 28 days for subsequent cycles as determined by totality
of data collected thus far including PK/Pharmacodynamics (PD), safety and preliminary
efficacy.

Active, not recruiting
Neoplasm Malignant

Drug: SAR442257

Pharmaceutical form: Sterile powder for reconstitution Route of administration:
Intravenous infusion

Eligibility Criteria

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 status ≤2.

RRMM patients:

must have received at least 3 prior lines of therapy including proteasome inhibitor (PI),
immunomodulatory agent (IMiD), and anti-CD38 mAb;

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; based upon investigator's clinical judgement.

and must not be candidates for regimens known to provide clinical benefit based upon
investigator's clinical judgement.

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 therapies; based upon investigator's clinical judgement.

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).

- HGBCL with MYC and/or BCL2 and/or BCL6 rearrangement or HGBCL NOS,

- 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)
including the following subtype of disease: Nodal peripheral TCL including
angio-immunoblastic TCL (AITL), anaplastic large cell lymphoma (ALCL), adult T cell
leukemia-lymphoma, and peripheral TCL NOS (not otherwise specified). Peripheral TCL
of the innate immune system: breast implant ALCL, extranodal NK/TCL, enteropathy
associated TCL, monomorphic epitheliotropic intestinal TCL, and hepatosplenic 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.
For post-CAR-T patients a fresh LN biopsy is expected if in a superficial node. For these
patients tissue materials should be made available for analysis during the study.
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.

Exclusion criteria:

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, chronic lymphocytic leukemia 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 treatment.

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
exclusion criteria.

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
study.

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

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Czechia
Korea, Republic of
Norway
Spain
United States
Locations

City of Hope Site Number : 8400001
Duarte, California, United States

University of Miami - Sylvester Comprehensive Cancer Center Site Number : 8400005
Miami, Florida, United States

Mayo Clinic of Rochester Site Number : 8400003
Rochester, Minnesota, United States

Investigational Site Number : 2030003
Brno, Czechia

Investigational Site Number : 2030001
Ostrava - Poruba, Czechia

Investigational Site Number : 2030002
Praha 2, Czechia

Investigational Site Number : 4100001
Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 4100002
Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 5780001
Oslo, Norway

Investigational Site Number : 5780101
Oslo, Norway

Investigational Site Number : 7240005
Santander, Cantabria, Spain

Investigational Site Number : 7240003
Badalona, Catalunya [Cataluña], Spain

Investigational Site Number : 7240006
Madrid, Madrid, Comunidad De, Spain

Investigational Site Number : 7240001
Pamplona, Navarra, Spain

Investigational Site Number : 7240007
Madrid, Spain

Investigational Site Number : 7240004
Valencia, Spain

Clinical Sciences & Operations, Study Director
Sanofi

NCT Number
MeSH Terms
Neoplasms