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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: SAR442257

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number : 2030003
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number : 2030001
  • Praha 2, Czechia, 12808
    • Investigational Site Number : 2030002
• Korea, Republic of
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 06351
      • Investigational Site Number : 4100002
• Norway
  • Oslo, Norway, 0440
    • Investigational Site Number : 5780001
  • Oslo, Norway, 0450
    • Investigational Site Number : 5780101
• Spain
  • Madrid, Spain, 28041
    • Investigational Site Number : 7240007
  • Valencia, Spain, 46026
    • Investigational Site Number : 7240004
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Investigational Site Number : 7240005
  • Catalunya [Cataluña]
    • Badalona, Catalunya [Cataluña], Spain, 08916
      • Investigational Site Number : 7240003
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28027
      • Investigational Site Number : 7240006
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Investigational Site Number : 7240001
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Site Number : 8400001
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Sylvester Comprehensive Cancer Center Site Number : 8400005
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic of Rochester Site Number : 8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; SAR442257 will be given intravenously with lead-in doses (LID) in the first-week, followed by once weekly until week 4 (Cycle 1) and once weekly for each subsequent cycle(s).	Drug: SAR442257; Pharmaceutical form: Sterile powder for reconstitution Route of administration: Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine maximum tolerated dose (MTD)	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%)	Baseline to estimated 4 weeks
Determine recommended Phase 2 dose (RP2D)	RP2D: defined as the dose selected for the further single agent testing in the future study	Baseline to estimated 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic (PK) parameter: Cmax	Maximum concentration observed (Cmax)	through study completion (estimated 16 months)
Assessment of PK parameter: Ctrough	Concentration observed just before treatment administration during repeated dosing (Ctrough)	through study completion (estimated 16 months)
Overall response rate for RRMM	Overall response rate will be assessed using the International Myeloma Working Group (IMWG) 2016 criteria for patients with RRMM	Baseline to 6 months
Overall response rate for RR-NHL	Overall response rate will be assessed using the Response evaluation criteria in lymphoma (RECIL) 2017 criteria for patients with RR-NHL	Baseline to 6 months
Number of participants with AEs/SAEs/AESI	Incidence of treatment-emergent adverse events (AEs)/serious adverse events (SAEs)/ adverse events of special interest (AESIs) and laboratory abnormalities	Baseline to 30 days after end of treatment
Assessment of PK parameter: AUC0-τ	Area under the concentration versus time curve during a dosing interval (T) (AUC0-τ)	up to 4 weeks
Incidence of anti-drug antibody (ADA)	Incidence of (ADA) against SAR442257	Baseline to 60 days after end of treatment

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2020
• Primary Completion (Actual): March 2, 2024
• Study Completion (Estimated): August 14, 2024

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TED16364; 2019-003390-26 (EudraCT Number); U1111-1244-2511 (Registry Identifier: UTN); 2023-508358-24 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• 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