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

NCT04401020 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: TED16364U1111-1244-25112023-508358-242019-003390-26
• Study Type: interventional
• Target: 47
• Locations: 5 countries
• Sites: 16

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 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 assess preliminary evidence of antitumor activity

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Number of participants with AEs/SAEs/AESI

  Baseline to 30 days after end of treatment

• Assessment of pharmacokinetic (PK) parameter: Cmax

  through study completion (estimated 16 months)

• Assessment of PK parameter: Ctrough

  through study completion (estimated 16 months)

• Assessment of PK parameter: AUC0-τ

  up to 4 weeks

• Overall response rate for RRMM

  Baseline to 6 months

Study Arms (1)

Dose escalation

EXPERIMENTAL

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

Interventions

SAR442257 DRUG

Pharmaceutical form: Sterile powder for reconstitution Route of administration: Intravenous infusion

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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),

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (16)

City of Hope Site Number : 8400001

Duarte, California, 91010, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center Site Number : 8400005

Miami, Florida, 33136, United States

Location

Mayo Clinic of Rochester Site Number : 8400003

Rochester, Minnesota, 55905, United States

Location

Investigational Site Number : 2030003

Brno, 62500, Czechia

Location

Investigational Site Number : 2030001

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030002

Prague, 12808, Czechia

Location

Investigational Site Number : 5780001

Oslo, 0440, Norway

Location

Investigational Site Number : 5780101

Oslo, 0450, Norway

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 7240005

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 7240003

Badalona, Catalunya [Cataluña], 08916, Spain

Location

Investigational Site Number : 7240006

Madrid, Madrid, Comunidad de, 28027, Spain

Location

Investigational Site Number : 7240001

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240007

Madrid, 28041, Spain

Location

Investigational Site Number : 7240004

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 26, 2020
• Study Start: July 24, 2020
• Primary Completion: March 2, 2024
• Study Completion: March 17, 2026
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (6); US (3); KR (2); NO (2); CZ (3)