A Study to Investigate Safety and Efficacy With SAR445514 in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and Relapsed/Refractory Light-chain Amyloidosis (RRLCA)

Last updated: June 9, 2025
Sponsor: Sanofi
Overall Status: Terminated

Phase

1/2

Condition

Bone Neoplasm

Red Blood Cell Disorders

Leukemia

Treatment

SAR445514

Clinical Study ID

NCT05839626
TCD17710
2022-502057-33-00
U1111-1279-2985
  • Ages > 18
  • All Genders

Study Summary

This is a first-in-human (FIH) Phase 1/Phase 2 study for evaluating SAR445514 in monotherapy in participants with relapsed/refractory multiple myeloma (RRMM) and relapsed/refractory light chain amyloidosis (RRLCA).

The study will comprise 3 parts:

A dose escalation phase (Part 1) in RRMM participants (Part 1a) that will evaluate several doses administered to determine 2 doses that will be tested in the dose optimization part.

A dose escalation will also be done in RRLCA participants (Part 1b) but started sequentially after the end of the dose escalation in RRMM participants. This dose escalation will evaluate the 2 doses planned to be used in dose optimization in RRMM, to ensure those doses are safe also for RRLCA participants.

A dose optimization phase (Part 2) that will be evaluating 2 doses determined from Part 1 to determine the preliminary recommended Phase 2 dose (pRP2D) and schedule for SAR445514 in RRMM.

A dose expansion phase (Part 3) that will evaluate the preliminary efficacy of pRP2D and schedule for SAR445514 in RRMM (Part 3a) and RRLCA (Part 3b).

Approximately 111 participants will be enrolled and treated by study intervention and separated as such:

Part 1a: Approximately 30 to 40 participants Part 1b: Approximately 6 to 12 participants Part 2: Approximately 30 participants Part 3a: Approximately 15 participants Part 3b: Approximately 14 participants

Eligibility Criteria

Inclusion

Inclusion Criteria:

Participants must have a documented diagnosis of multiple myeloma (Part 1a, 2, and 3a) or light chain amyloidosis (Part 1b and 3b).

Participants with RRMM (Part 1, 2, and 3a)

  • Participants with measurable disease for RRMM

  • Participants with MM must have received at least 2 prior lines of therapy which mustinclude at least 2 consecutive cycles of a second or third generationimmunomodulator, steroid, proteasome inhibitor and anti-CD38 monoclonal antibody (MoAb).

  • Participants must have documented evidence of progressive disease (PD), as per IMWG 2016 criteria.

Participants with RR LCA (Part 1b and 3b) must have received at least 1 prior line of treatment comprising at least 1 proteasome inhibitor.

  • Participants with measurable disease according to ISA 2012.

  • Participants must have documented evidence of progressive disease (PD), as per ISA 2012 criteria.

  • One or more organ impacted by amyloidosis as per National comprehensive cancernetwork (NCCN) guidelines.

For dose escalation, body weight within 40 to 120 kg

Capable of giving signed informed consent

Exclusion

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Medical conditions

  • Primary refractory MM defined as participants who never achieved at least a minimalresponse with any treatment during the disease course

  • Second primary malignancy

Participants with RRMM (Part 1a, 2, and 3a)

  • For MM participants, primary systemic LCA and plasma cell leukemia

  • For MM participants, congestive heart failure (New York Heart Association [NYHA])Grade ≥II; cardiomyopathy, active ischemia, or any other uncontrolled cardiaccondition

Participants with RR LCA (Part 1b and 3b)

  • For LCA participants, evidence of clinically significant cardiovascular condition,defined as one or more of the following:
  1. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >8500 ng/mL

  2. New York Heart Association (NYHA) classification III or IV heart failure

  3. Heart failure that, in the opinion of the Investigator, is not primarilyrelated to LCA cardiomyopathy (including, but not limited to, ischemic heartdisease, uncorrected valvular disease, infections)

  4. Prior event (history) in the last 6 months of acute coronary syndrome,myocardial infarction or unstable angina as well as participants who during thelast 6 months experienced a percutaneous cardiac intervention with stent and/ora coronary artery bypass

  5. Hospitalization in the last 4 weeks prior to treatment related to acardiovascular event

  6. Participants with prior history of arrhythmia and/or cardiac conductiondisorders for which a pacemaker or an implantable cardioverter defibrillator (ICD) is required but has not been placed. This includes, but may not belimited to, sustained ventricular tachycardia, association of anatrioventricular, or sinoatrial nodal dysfunction

  • For LCA participants, a systolic blood pressure <100 mmHg or a diastolic bloodpressure <55 mmHg.

  • For LCA participants: previous or current diagnosis of symptomatic MM, including thepresence of lytic bone disease, plasmacytomas, ≥60% plasma cells in the BM, orhypercalcemia.

All participants

  • Uncontrolled infection within 14 days prior to study treatment.

  • Known acquired immunodeficiency syndrome-related illness or known humanimmunodeficiency virus (HIV) disease requiring antiviral treatment or activehepatitis A (defined as positive hepatitis A antigen or positive IgM); HIV serologyat screening will be tested for participants in countries where it is required bylocal regulations.

  • Uncontrolled or active hepatitis B virus (HBV) infection: participants with positiveB surface antigen (HBsAg) and/or HBV deoxyribonucleic acid (DNA)

  • Active hepatitis C virus (HCV) infection: positive HCV ribonucleic acid (RNA) andnegative anti-HCV.

Prior/concomitant therapy

  • Any anti-MM drug treatment within 14 days before study treatment

  • Prior allogenic hematopoietic stem cell (HSC) transplant with activegraft-versus-host disease (GvHD) (GvHD any grade and/or being underimmunosuppressive treatment within the last 2 months prior to first IMP).

  • Any major procedure within 14 days before the initiation of the study treatment

  • Administration of an anti-CD38 monoclonal antibody (isatuximab or daratumumab) lessthan 90 days prior to the first administration of study treatment.

  • Administration of an anti-BCMA agent (including, but not limited to, CAR T-cells,TCEs, antibody drug conjugate) less than 21 days prior to the administration ofstudy treatment.

  • Unresolved toxicities from prior anticancer therapy, defined as not having resolvedto CTCAE Version 5.0 Grade 1, at the exception of residual Grade 2 peripheralneurotoxicity related to bortezomib and/or thalidomide and considered as stable.

  • Participants with a contraindication to dexamethasone.

Prior/concurrent clinical study experience

  • Received any other investigational drugs or prohibited therapy for this study within 28 days or 5 half-lives from study treatment, whichever is shorter

Diagnostic assessments

  • Hemoglobin <8 g/dL (5.0 mmol/L)

  • Platelets <50 × 10^9/L (not permissible to transfuse a participant within 1 weekprior to the screening platelet count to reach this level).

  • Absolute neutrophil count (ANC) <1000 μL (1 × 10^9/L).

  • Creatinine clearance <30 mL/min (Modification of Diet in Renal Disease Formula).

  • Total bilirubin >1.5 × upper limit of normal (ULN) (unless the subject hasdocumented Gilbert syndrome in which case direct bilirubin should not be >2.5 ×ULN).

  • Aspartate aminotransferase (AST/SGOT) or Alanine aminotransferase (ALT/SGPT) >2.5 ×ULN.

  • Participants with Grade 3 or 4 hypercalcemia (corrected serum calcium of >12.5mg/dL; >3.1 mmol/L; ionized calcium >1.6 mmol/L; or requiring hospitalization) willnot be eligible unless participants recover to Grade 2 or less underanti-hypercalcemia treatment.

Other exclusions

  • Individuals accommodated in an institution because of regulatory or legal order;prisoners or participants who are legally institutionalized

  • Participant not suitable for participation, whatever the reason, as judged by theInvestigator

  • Sensitivity to any of the study interventions, or components thereof, or drug orother allergy that, in the opinion of the Investigator, contraindicatesparticipation in the study.

Study Design

Total Participants: 32
Treatment Group(s): 1
Primary Treatment: SAR445514
Phase: 1/2
Study Start date:
May 15, 2023
Estimated Completion Date:
May 26, 2025

Study Description

The duration of the study for a participant will include A screening period: up to 28 days prior day 1 of cycle 1 (C1D1) A treatment period: enrolled participants will receive administration of 4 weeks cycles of SAR445514 subcutaneously.

The End of treatment visit will occur 30 days (+/- 7 days) from last investigational medicinal product (IMP) administration or prior initiation of further therapy, whichever comes first.

The follow-up period will continue until death, participant's request to discontinue study, final Overall Survival analysis or upon cancellation of survival follow-up at the discretion of the Sponsor at any timepoint.

Connect with a study center

  • Investigational Site Number : 0360001

    Wollongong, New South Wales 2500
    Australia

    Site Not Available

  • Investigational Site Number :0360001

    Wollongong, New South Wales 2500
    Australia

    Active - Recruiting

  • Investigational Site Number : 0360002

    Richmond, Victoria 3121
    Australia

    Site Not Available

  • Investigational Site Number :0360002

    Richmond, Victoria 3121
    Australia

    Active - Recruiting

  • Institut Jules Bordet_Site Number : 0560002

    Anderlecht, 1070
    Belgium

    Site Not Available

  • Investigational Site Number : 0560002

    Anderlecht, 1070
    Belgium

    Active - Recruiting

  • Investigational Site Number :0560002

    Anderlecht, 1070
    Belgium

    Active - Recruiting

  • Investigational Site Number : 0560001

    Antwerp, 2060
    Belgium

    Site Not Available

  • Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Cadix_Site Number : 0560001-1

    Antwerpen, 2030
    Belgium

    Site Not Available

  • Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Middelheim_Site Number : 0560001-2

    Antwerpen, 2020
    Belgium

    Site Not Available

  • Investigational Site Number : 0560001

    Antwerpen, 2030
    Belgium

    Active - Recruiting

  • Investigational Site Number :0560001

    Antwerpen, 2060
    Belgium

    Active - Recruiting

  • Investigational Site Number : 2030002

    Brno, 625 00
    Czechia

    Site Not Available

  • Investigational Site Number : 2030001

    Ostrava, 708 52
    Czechia

    Site Not Available

  • Investigational Site Number : 2030001

    Ostrava - Poruba, 70852
    Czechia

    Site Not Available

  • Investigational Site Number : 3480001

    Budapest, 1085
    Hungary

    Site Not Available

  • Investigational Site Number : 3800001

    Rozzano, Lombardia 20089
    Italy

    Site Not Available

  • Investigational Site Number : 7240003

    Barcelona, Barcelona [Barcelona] 08036
    Spain

    Active - Recruiting

  • Investigational Site Number :7240003

    Barcelona, Barcelona [Barcelona] 08036
    Spain

    Active - Recruiting

  • Hospital Universitario Marqués de Valdecilla_Site Number : 7240001

    Santander, Cantabria 39008
    Spain

    Site Not Available

  • Investigational Site Number : 7240001

    Santander, Cantabria 39008
    Spain

    Active - Recruiting

  • Investigational Site Number :7240001

    Santander, Cantabria 39008
    Spain

    Active - Recruiting

  • Investigational Site Number : 7240002

    Badalona, Catalunya [Cataluña] 08916
    Spain

    Active - Recruiting

  • Institut Catala d´oncologia - Badalona_Site Number : 7240002

    Badalona, Cataluña 08916
    Spain

    Site Not Available

  • HOSPITAL CLINIC i PROVINCIAL BARCELONA_Site Number : 7240003

    Barcelona, 08036
    Spain

    Site Not Available

  • Investigational Site Number : 8260003

    Birmingham, B15 2TH
    United Kingdom

    Site Not Available

  • Investigational Site Number : 8260002

    London, NW1 2BU
    United Kingdom

    Site Not Available

  • Investigational Site Number :8260002

    London, WC1N3BG
    United Kingdom

    Active - Recruiting

  • Investigational Site Number : 8260001

    Manchester, M20 4BX
    United Kingdom

    Site Not Available

  • Investigational Site Number :8260001

    Manchester, M20 4BX
    United Kingdom

    Active - Recruiting

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