First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL

Brief description of study

Primary Objective:

To determine the maximum tolerated dose (MTD) of SAR442257 administered as a single agent in patients with relapsed and refractory multiple myeloma (RRMM) and relapsed and refractory 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 evaluate the potential immunogenicity of SAR442257
  • To assess preliminary evidence of antitumor activity

Detailed description of study

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.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Neoplasm Malignant
  • Age: 18 Years
  • Gender: Male or Female

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

Updated on 21 Feb 2023 . Study ID: NCT04401020

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