Clinical Trials /

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

NCT04401020

Description:

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 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

Related Conditions:
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TED16364
  • SECONDARY ID: 2019-003390-26
  • SECONDARY ID: U1111-1244-2511
  • NCT ID: NCT04401020

Conditions

  • Neoplasm Malignant

Interventions

DrugSynonymsArms
SAR442257Dose escalation
Acetaminophen or equivalent (premedication)Dose escalation
Ranitidine or equivalent (premedication)Dose escalation
Diphenhydramine or equivalent (premedication)Dose escalation
Montelukast (premedication)Dose escalation
Dexamethasone (premedication)Dose escalation

Purpose

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 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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalationExperimentalSAR442257 will be given intravenously with lead-in doses (LID) in the first-week, followed by twice weekly until week 4 (Cycle 1) and twice weekly for each subsequent cycle(s).
  • SAR442257
  • Acetaminophen or equivalent (premedication)
  • Ranitidine or equivalent (premedication)
  • Diphenhydramine or equivalent (premedication)
  • Montelukast (premedication)
  • Dexamethasone (premedication)

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 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
        benefit.

        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 (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.

        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
        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
        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine maximum tolerated dose (MTD)
Time Frame:Baseline to estimated 4 weeks
Safety Issue:
Description:MTD: defined as the highest dose level (DL) with highest probability of Investigational Medicinal Product (IMP)-related dose limiting toxicity (DLT) rate within the target range (16 to 33%) among dose levels with less than 0.25 probability of DLT rate above target (>33%)

Secondary Outcome Measures

Measure:Number of participants with AEs/SAEs/AESI
Time Frame:Baseline to 30 days after end of treatment
Safety Issue:
Description:Incidence of treatment-emergent adverse events (AEs)/serious adverse events (SAEs)/ adverse events of special interest (AESIs)
Measure:Assessment of pharmacokinetic (PK) parameter: Cmax
Time Frame:through study completion (estimated 16 months)
Safety Issue:
Description:Maximum concentration observed (Cmax)
Measure:Assessment of PK parameter: Ctrough
Time Frame:through study completion (estimated 16 months)
Safety Issue:
Description:Concentration observed just before treatment administration during repeated dosing (Ctrough)
Measure:Assessment of PK parameter: AUC0-τ
Time Frame:up to 5 weeks
Safety Issue:
Description:Area under the concentration versus time curve during a dosing interval (T) (AUC0-τ)
Measure:Incidence of anti-drug antibody (ADA)
Time Frame:Baseline to 30 days after end of treatment
Safety Issue:
Description:Incidence of (ADA) against SAR442257
Measure:Overall response rate for RRMM
Time Frame:Baseline to 6 months
Safety Issue:
Description:Overall response rate will be assessed using the International Myeloma Working Group (IMWG) 2016 criteria for patients with RRMM
Measure:Overall response rate for RR-NHL
Time Frame:Baseline to 6 months
Safety Issue:
Description:Overall response rate will be assessed using the Response evaluation criteria in lymphoma (RECIL) 2017 criteria for patients with RR-NHL

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

August 18, 2020