Clinical Trials /

First-in-human Single Agent Study of SAR442085 in Relapsed or Refractory Multiple Myeloma

NCT04000282

Description:

Primary Objectives: - Dose Escalation Part A: To determine the maximum tolerated dose (MTD) of SAR442085 administered as a single agent in patients with relapsed or refractory multiple myeloma (RRMM), and determine the recommended Phase 2 dose (RP2D) for the subsequent Expansion Part B - Dose Expansion Part B: To assess the antitumor activity of single agent of SAR442085 at the RP2D in patients with RRMM Secondary Objectives: - To characterize the safety profile of SAR442085 - To characterize the pharmacokinetics (PK) profile of SAR442085 when administered as a single agent - To evaluate the potential immunogenicity of SAR442085 - To assess preliminary evidence of antitumor activity in the Dose Escalation Part A

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Single Agent Study of SAR442085 in Relapsed or Refractory Multiple Myeloma
  • Official Title: An Open-label, First-in-human, Single Agent, Dose-escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR442085 in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

Clinical Trial IDs

  • ORG STUDY ID: TED16132
  • SECONDARY ID: 2019-001018-40
  • SECONDARY ID: U1111-1223-4410
  • NCT ID: NCT04000282

Conditions

  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
SAR442085Part B: SAR442085 dose expansion

Purpose

Primary Objectives: - Dose Escalation Part A: To determine the maximum tolerated dose (MTD) of SAR442085 administered as a single agent in patients with relapsed or refractory multiple myeloma (RRMM), and determine the recommended Phase 2 dose (RP2D) for the subsequent Expansion Part B - Dose Expansion Part B: To assess the antitumor activity of single agent of SAR442085 at the RP2D in patients with RRMM Secondary Objectives: - To characterize the safety profile of SAR442085 - To characterize the pharmacokinetics (PK) profile of SAR442085 when administered as a single agent - To evaluate the potential immunogenicity of SAR442085 - To assess preliminary evidence of antitumor activity in the Dose Escalation Part A

Detailed Description

      Patient will continue to receive study medication until disease progression, unacceptable
      toxicity, withdrawal of informed consent, or other reason why investigator considers it
      appropriate to discontinue study medication. Once permanently discontinued, study medication
      cannot be restarted at later timepoint.
    

Trial Arms

NameTypeDescriptionInterventions
Part A: SAR442085 dose escalationExperimentalSAR442085 will be given intravenously weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle until the patient has progressive disease, unacceptable toxicity or other reasons to terminate study treatment. Each cycle will be approximately 28 days in duration.
  • SAR442085
Part B: SAR442085 dose expansionExperimentalSAR442085 will be given intravenously weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle until the patient has progressive disease, unacceptable toxicity or other reasons to terminate study treatment. Each cycle will be approximately 28 days in duration.
  • SAR442085

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.

          -  Participant has given voluntary written informed consent.

          -  Participant has been previousy diagnosed with multiple myeloma based on standard
             criteria.

          -  Part A: (1) participant has received at least 3 prior lines of therapy for multiple
             myeloma, or at least 2 prior lines of therapy if at least 1 of those lines consisted
             of 2 or more multi-agent regimens (eg, multi-agent induction regimen with autologous
             stem cell transplantation, followed by maintenance regimen). (2) Prior therapy for
             multiple myeloma has included at least 1 proteasome inhibitor (bortezomib,
             carfilzomib, ixazomib), at least 1 immunomodulatory agent (lenalidomide, thalidomide,
             pomalidomide), at least 1 anti-CD38 monoclonal antibody and at least 1 steroid. (3)
             Participant had at least a minimal response (MR) to the anti-CD38 antibody containing
             regimen and had last dose of anti-CD38 monoclonal antibody at least 9 months prior to
             study entry, except the last cohort(s) of Part A who are anti CD38 naïve.

          -  Part B and the last cohort(s) of Part A: (1) participant has received at least 3 prior
             lines of therapy for multiple myeloma, or at least 2 prior line of therapy if at least
             1 of those lines consisted of 2 or more multi-agent regimens (eg, multi-agent
             induction regimen with autologous stem cell transplantation, followed by maintenance
             regimen). (2) Prior therapy for multiple myeloma has included at least 1 proteasome
             inhibitor (bortezomib, carfilzomib, ixazomib), at least 1 immunomodulatory agent
             (lenalidomide, thalidomide, pomalidomide) and at least 1 steroid. (3) Prior therapy
             has not included an anti-CD38 monoclonal antibody.

          -  Participant has myeloma disease progression on or after last therapy.

          -  Participant must have measurable disease as defined as at least one of the following:

               -  Serum M protein ≥0.5 g/dL (≥5 g/L)

               -  Urine M protein ≥200 mg/24 hours

               -  Serum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum

               -  FLC ratio (<0.26 or >1.65).

          -  A male participant must agree to use contraception during the intervention period and
             for at least 150 days after the last dose of study drug and refrain from donating
             sperm during this period.

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               -  Not a woman of childbearing potential (WOCBP)

               -  A WOCBP who agrees to follow the contraceptive guidance during the intervention
                  period and for at least 150 days after the last dose of study intervention.

        Exclusion criteria:

          -  Participant is diagnosed or treated for another malignancy within 3 years prior to
             enrollment, with the exception of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, superficial bladder carcinoma or low risk prostate
             cancer.

          -  Participant has an Eastern Cooperative Oncology Group (ECOG) performance status score
             >2.

          -  Participant has a history of Chronic obstructive pulmonary disease (COPD) or asthma.

          -  Participant has not recovered from adverse reactions to prior myeloma treatment or
             procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade ≤1 or
             baseline (exception: alopecia).

          -  Participant has congestive heart failure (New York Heart Association) Grade ≥II;
             cardiac myopathy, 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).

          -  Participant has had acute myocardial infarction within 6 months before first dose of
             study medication.

          -  Participant has ongoing sensory or motor neuropathy of National Cancer Institute
             Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥3.

          -  Participant 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.

          -  Known acquired immunodeficiency syndrome (AIDS) or related illnesses or human
             immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or to have
             active hepatitis A, B (defined as a known positive hepatitis B surface antigen (HBsAg)
             result), or C (defined as a known quantitative hepatitis C [HCV] ribonucleic acid RNA
             results greater than the lower limits of detection of the assay or positive HCV
             antigen) infection.

          -  Participant has positive Coombs test at baseline.

        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:The maximum tolerated dose (MTD) of SAR442085 (Part A)
Time Frame:At the end of Cycle 1 (each cycle is approximately 28 days)
Safety Issue:
Description:MTD is defined as the dose level 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:Treatment-emergent adverse events (AEs)/serious adverse events (SAE) (Both Part A and B)
Time Frame:From baseline to end of treatment + 30 days (approx. 2 years)
Safety Issue:
Description:Number of participants with Treatment-Emergent Adverse events (TEAEs) from baseline to End of Study.
Measure:PK parameters of SAR442085: Cmax (Both Part A and B)
Time Frame:Cycle 1 Day 1 to Day 28
Safety Issue:
Description:Maximum plasma concentration observed (Cmax).
Measure:PK parameters of SAR442085: Tmax (Both Part A and B)
Time Frame:Cycle 1 Day 1 to Day 28
Safety Issue:
Description:First time to reach Cmax (tmax).
Measure:PK parameters of SAR442085: AUC (Both Part A and B)
Time Frame:Cycle 1 Day 1 to Day 28
Safety Issue:
Description:Area under the plasma concentration versus time curve extrapolated to infinity (AUC).
Measure:Anti-drug antibody (ADA) against SAR442085 (Both Part A and B)
Time Frame:Cycle 1, 2, 3, 6 and 9 (each cycle is approximately 28 days)
Safety Issue:
Description:Number of participants with ADA against SAR442085.
Measure:Progression-free survival (Part B)
Time Frame:approximately 12 months after the last patient has started treatment in Part B (approx. 2 years)
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time interval from the date of enrollment to the date of documented tumor progression as per IMWG or death (due to any cause), whichever comes first.
Measure:Duration of response (Part B)
Time Frame:approximately 12 months after the last patient has started treatment in Part B (approx. 2 years)
Safety Issue:
Description:Duration of response (DOR) is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as per IMWG or death from any cause, whichever occurs first.

Details

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

Last Updated

November 18, 2019