Phase
Condition
Bone Neoplasm
Red Blood Cell Disorders
Leukemia
Treatment
SAR445514
Clinical Study ID
Ages > 18 All Genders
Study Summary
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:
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >8500 ng/mL
New York Heart Association (NYHA) classification III or IV heart failure
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)
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
Hospitalization in the last 4 weeks prior to treatment related to acardiovascular event
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
Study Description
Connect with a study center
Investigational Site Number : 0360001
Wollongong, New South Wales 2500
AustraliaSite Not Available
Investigational Site Number :0360001
Wollongong, New South Wales 2500
AustraliaActive - Recruiting
Investigational Site Number : 0360002
Richmond, Victoria 3121
AustraliaSite Not Available
Investigational Site Number :0360002
Richmond, Victoria 3121
AustraliaActive - Recruiting
Institut Jules Bordet_Site Number : 0560002
Anderlecht, 1070
BelgiumSite Not Available
Investigational Site Number : 0560002
Anderlecht, 1070
BelgiumActive - Recruiting
Investigational Site Number :0560002
Anderlecht, 1070
BelgiumActive - Recruiting
Investigational Site Number : 0560001
Antwerp, 2060
BelgiumSite Not Available
Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Cadix_Site Number : 0560001-1
Antwerpen, 2030
BelgiumSite Not Available
Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Middelheim_Site Number : 0560001-2
Antwerpen, 2020
BelgiumSite Not Available
Investigational Site Number : 0560001
Antwerpen, 2030
BelgiumActive - Recruiting
Investigational Site Number :0560001
Antwerpen, 2060
BelgiumActive - Recruiting
Investigational Site Number : 2030002
Brno, 625 00
CzechiaSite Not Available
Investigational Site Number : 2030001
Ostrava, 708 52
CzechiaSite Not Available
Investigational Site Number : 2030001
Ostrava - Poruba, 70852
CzechiaSite Not Available
Investigational Site Number : 3480001
Budapest, 1085
HungarySite Not Available
Investigational Site Number : 3800001
Rozzano, Lombardia 20089
ItalySite Not Available
Investigational Site Number : 7240003
Barcelona, Barcelona [Barcelona] 08036
SpainActive - Recruiting
Investigational Site Number :7240003
Barcelona, Barcelona [Barcelona] 08036
SpainActive - Recruiting
Hospital Universitario Marqués de Valdecilla_Site Number : 7240001
Santander, Cantabria 39008
SpainSite Not Available
Investigational Site Number : 7240001
Santander, Cantabria 39008
SpainActive - Recruiting
Investigational Site Number :7240001
Santander, Cantabria 39008
SpainActive - Recruiting
Investigational Site Number : 7240002
Badalona, Catalunya [Cataluña] 08916
SpainActive - Recruiting
Institut Catala d´oncologia - Badalona_Site Number : 7240002
Badalona, Cataluña 08916
SpainSite Not Available
HOSPITAL CLINIC i PROVINCIAL BARCELONA_Site Number : 7240003
Barcelona, 08036
SpainSite Not Available
Investigational Site Number : 8260003
Birmingham, B15 2TH
United KingdomSite Not Available
Investigational Site Number : 8260002
London, NW1 2BU
United KingdomSite Not Available
Investigational Site Number :8260002
London, WC1N3BG
United KingdomActive - Recruiting
Investigational Site Number : 8260001
Manchester, M20 4BX
United KingdomSite Not Available
Investigational Site Number :8260001
Manchester, M20 4BX
United KingdomActive - Recruiting
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