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;
• Must have received their last dose of prior anti-CD38 therapy within 12 months prior to the first dose of SAR442257;
• Must be refractory to anti-CD38 antibody (e.g., daratumumab or isatuximab), characterized by progression within 60 days of the last dose of anti-CD38, regardless of which line it was given;
• 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;
• 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.
• 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 (i.e., 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.
• Male participants are eligible to participate if they agree to the following starting from the time of informed consent, during the treatment period, and for at least 180 days after the last dose of study intervention:
  • Refrain from donating sperm.  Plus either: Be abstinent from heterosexual intercourse (abstinent on a long term and persistent basis) and agree to remain abstinent; OR
  • Must agree to use contraception/barrier;
  • Agree to use a male condom when having sexual intercourse with a woman of childbearing potential who is not currently pregnant;
  • Female participants A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential; OR
  • Is a woman of childbearing potential and agrees to use two highly effective contraceptive methods with a failure rate of < 1% per year starting from the time of informed consent, during the treatment period, and for at least 180 days after the last dose of study intervention;
  • A woman of childbearing potential must have a negative highly sensitive pregnancy test (serum) within 7 days before the first dose of study intervention.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Capable of giving signed informed consent of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

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, leukemic manifestations of lymphoma, chronic lymphocytic leukemia, and prolymphocytic leukemia.
• Known 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). E 08. Known positivity for Human Immunodeficiency Virus (HIV). E 09. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to 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.
• Autologous stem cell transplantation (SCT) within 100 days prior to first study treatment, or any prior allogeneic SCT or solid organ transplantation, any one or more of the following: systemic immunosuppressive therapy within 3 months prior to start study treatment, any active acute graft versus host disease (GvHD), Grade 2-4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment.
• Systemic radiation therapy < 28 days and focal radiotherapy < 14 days prior to the first dose administration of SAR442257.
•  Major surgery, defined as surgery requiring general anesthesia with endotracheal intubation within 28 days prior to the first dose administration of SAR442257, unless discussed with and eligibility approved by sponsor medical monitor.
• Participant received any investigational drug within 5 half-lives (of the investigational drug) or within 21 days of the first dose of SAR442257, whichever is shorter.
• Dexamethasone at cumulative doses of greater than 160 mg or equivalent < 3 weeks prior to the first dose administration of SAR442257 is not allowed. Use of topical or inhaled steroids is acceptable.
• Concomitant oral anticoagulant therapy or low molecular weight heparin (LMWH) (low dose aspirin is allowed).
• Participants are excluded if they received a live vaccine within 6 weeks prior to the first SAR442257 administration.

Eligibility last updated 1/11/22. Questions regarding updates should be directed to the study team contact.