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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04401020
Recruitment Status : Recruiting
First Posted : May 26, 2020
Last Update Posted : January 6, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

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


Condition or disease Intervention/treatment Phase
Neoplasm Malignant Drug: SAR442257 Drug: Acetaminophen or equivalent (premedication) Drug: Ranitidine or equivalent (premedication) Drug: Diphenhydramine or equivalent (premedication) Drug: Montelukast (premedication) Drug: Dexamethasone (premedication) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 24, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose escalation
SAR442257 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).
Drug: SAR442257
Pharmaceutical form: Sterile lyophilized powder for reconstitution Route of administration: Intravenous infusion

Drug: Acetaminophen or equivalent (premedication)
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Ranitidine or equivalent (premedication)
Pharmaceutical form: Solution for injection or Tablet Route of administration: Intravenous or Oral

Drug: Diphenhydramine or equivalent (premedication)
Pharmaceutical form: Solution for injection or Tablet Route of administration: Intravenous or Oral

Drug: Montelukast (premedication)
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Dexamethasone (premedication)
Pharmaceutical form: Solution for injection or Tablet Route of administration: Intravenous or Oral




Primary Outcome Measures :
  1. Determine maximum tolerated dose (MTD) [ Time Frame: Baseline to estimated 4 weeks ]
    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%)

  2. Determine recommended Phase 2 dose (RP2D) [ Time Frame: Baseline to estimated 4 months ]
    RP2D: defined as the dose selected for the further single agent testing in the future study


Secondary Outcome Measures :
  1. Number of participants with AEs/SAEs/AESI [ Time Frame: Baseline to 30 days after end of treatment ]
    Incidence of treatment-emergent adverse events (AEs)/serious adverse events (SAEs)/ adverse events of special interest (AESIs)

  2. Assessment of pharmacokinetic (PK) parameter: Cmax [ Time Frame: through study completion (estimated 16 months) ]
    Maximum concentration observed (Cmax)

  3. Assessment of PK parameter: Ctrough [ Time Frame: through study completion (estimated 16 months) ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough)

  4. Assessment of PK parameter: AUC0-τ [ Time Frame: up to 5 weeks ]
    Area under the concentration versus time curve during a dosing interval (T) (AUC0-τ)

  5. Incidence of anti-drug antibody (ADA) [ Time Frame: Baseline to 30 days after end of treatment ]
    Incidence of (ADA) against SAR442257

  6. Overall response rate for RRMM [ Time Frame: Baseline to 6 months ]
    Overall response rate will be assessed using the International Myeloma Working Group (IMWG) 2016 criteria for patients with RRMM

  7. Overall response rate for RR-NHL [ Time Frame: Baseline to 6 months ]
    Overall response rate will be assessed using the Response evaluation criteria in lymphoma (RECIL) 2017 criteria for patients with RR-NHL



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401020


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, California
Investigational Site Number 8400001 Recruiting
Duarte, California, United States, 91010
United States, Minnesota
Investigational Site Number 8400003 Recruiting
Rochester, Minnesota, United States, 55905
Korea, Republic of
Investigational Site Number 4100001 Recruiting
Seoul, Korea, Republic of, 03080
Investigational Site Number 4100002 Recruiting
Seoul, Korea, Republic of, 06351
Spain
Investigational Site Number 7240003 Recruiting
Badalona, Spain, 08916
Investigational Site Number 7240001 Recruiting
Pamplona, Spain, 31008
Investigational Site Number 7240002 Recruiting
Salamanca, Spain, 37007
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04401020    
Other Study ID Numbers: TED16364
2019-003390-26 ( EudraCT Number )
U1111-1244-2511 ( Other Identifier: UTN )
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: January 6, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neoplasms
Acetaminophen
Diphenhydramine
Promethazine
Dexamethasone
Ranitidine
Ranitidine bismuth citrate
Montelukast
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Antipyretics
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action