Trial Title:
A Study to Investigate Safety and Efficacy With SAR445514 in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and Relapsed/Refractory Light-chain Amyloidosis (RRLCA)
NCT ID:
NCT05839626
Condition:
Relapsed/Refractory Multiple Myeloma
Amyloid Light-chain Amyloidosis
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SAR445514
Description:
Powder for solution for injection. Sub Cutaneous administration.
Arm group label:
SAR445514 Dose level A (part 2)
Arm group label:
SAR445514 Dose level B (part 2)
Arm group label:
SAR445514 RRLCA Dose escalation phase (part 1b)
Arm group label:
SAR445514 RRLCA Dose expansion (part 3b)
Arm group label:
SAR445514 RRMM Dose escalation phase (Part 1a)
Arm group label:
SAR445514 RRMM Dose expansion (part 3a)
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
Detailed 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.
Criteria for eligibility:
Criteria:
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 must
include at least 2 consecutive cycles of a second or third generation
immunomodulator, 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 cancer
network (NCCN) guidelines.
For dose escalation, body weight within 40 to 120 kg
Capable of giving signed informed consent
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 minimal
response 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 cardiac
condition
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 primarily
related to LCA cardiomyopathy (including, but not limited to, ischemic heart
disease, 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 the
last 6 months experienced a percutaneous cardiac intervention with stent and/or
a coronary artery bypass
5. Hospitalization in the last 4 weeks prior to treatment related to a
cardiovascular event
6. Participants with prior history of arrhythmia and/or cardiac conduction
disorders for which a pacemaker or an implantable cardioverter defibrillator
(ICD) is required but has not been placed. This includes, but may not be
limited to, sustained ventricular tachycardia, association of an
atrioventricular, or sinoatrial nodal dysfunction
- For LCA participants, a systolic blood pressure <100 mmHg or a diastolic blood
pressure <55 mmHg.
- For LCA participants: previous or current diagnosis of symptomatic MM, including the
presence of lytic bone disease, plasmacytomas, ≥60% plasma cells in the BM, or
hypercalcemia.
All participants
- Uncontrolled infection within 14 days prior to study treatment.
- Known acquired immunodeficiency syndrome-related illness or known human
immunodeficiency virus (HIV) disease requiring antiviral treatment or active
hepatitis A (defined as positive hepatitis A antigen or positive IgM); HIV serology
at screening will be tested for participants in countries where it is required by
local regulations.
- Uncontrolled or active hepatitis B virus (HBV) infection: participants with positive
B surface antigen (HBsAg) and/or HBV deoxyribonucleic acid (DNA)
- Active hepatitis C virus (HCV) infection: positive HCV ribonucleic acid (RNA) and
negative anti-HCV.
Prior/concomitant therapy
- Any anti-MM drug treatment within 14 days before study treatment
- Prior allogenic hematopoietic stem cell (HSC) transplant with active
graft-versus-host disease (GvHD) (GvHD any grade and/or being under
immunosuppressive 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) less
than 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 of
study treatment.
- Unresolved toxicities from prior anticancer therapy, defined as not having resolved
to CTCAE Version 5.0 Grade 1, at the exception of residual Grade 2 peripheral
neurotoxicity 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 week
prior 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 has
documented 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 >12.5
mg/dL; >3.1 mmol/L; ionized calcium >1.6 mmol/L; or requiring hospitalization) will
not be eligible unless participants recover to Grade 2 or less under
anti-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 the
Investigator
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Investigational Site Number : 0360001
Address:
City:
Wollongong
Zip:
2500
Country:
Australia
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 0360002
Address:
City:
Richmond
Zip:
3121
Country:
Australia
Status:
Recruiting
Facility:
Name:
Institut Jules Bordet_Site Number : 0560002
Address:
City:
Anderlecht
Zip:
1070
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Ellen De Cuyper
Phone:
0032 2 541 35 98
Email:
ellen.decuyper@hubruxelles.be
Investigator:
Last name:
Fabio ANDREOZZI
Email:
Principal Investigator
Facility:
Name:
Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Middelheim_Site Number : 0560001-2
Address:
City:
Antwerpen
Zip:
2020
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Erwin Janssen
Phone:
0032 3 217 74 24
Email:
erwin.janssen@zna.be
Investigator:
Last name:
Ka Lung WU
Email:
Principal Investigator
Facility:
Name:
Het Ziekenhuisnetwerk Antwerpen vzw - ZNA Cadix_Site Number : 0560001-1
Address:
City:
Antwerpen
Zip:
2030
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Karen Cox
Phone:
0032 3 339 76 38
Email:
karen.cox@zna.be
Investigator:
Last name:
Ka Lung WU
Email:
Principal Investigator
Facility:
Name:
Investigational Site Number : 0560001
Address:
City:
Antwerp
Zip:
2060
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 2030002
Address:
City:
Brno
Zip:
625 00
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 2030001
Address:
City:
Ostrava
Zip:
708 52
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 3480001
Address:
City:
Budapest
Zip:
1085
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 3800001
Address:
City:
Rozzano
Zip:
20089
Country:
Italy
Status:
Recruiting
Facility:
Name:
Hospital Universitario Marqués de Valdecilla_Site Number : 7240001
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Paula Lada Salvador
Phone:
0034 942 31 53 21
Email:
plada@idival.org
Investigator:
Last name:
Enrique Ocio San Miguel
Email:
Principal Investigator
Facility:
Name:
Institut Catala d´oncologia - Badalona_Site Number : 7240002
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Guillem Tur i Valles
Phone:
0034634758904
Email:
gtur@igtp.cat
Investigator:
Last name:
Albert Oriol Rocafiguera
Email:
Principal Investigator
Facility:
Name:
HOSPITAL CLINIC i PROVINCIAL BARCELONA_Site Number : 7240003
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Felipe Diaz Gomez
Phone:
0034 932275428
Email:
fadiaz@recerca.clinic.cat
Investigator:
Last name:
Carlos Fernandez de Larrea Rodriguez
Email:
Principal Investigator
Facility:
Name:
Investigational Site Number : 8260003
Address:
City:
Birmingham
Zip:
B15 2TH
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 8260002
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Investigational Site Number : 8260001
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Start date:
May 15, 2023
Completion date:
April 7, 2028
Lead sponsor:
Agency:
Sanofi
Agency class:
Industry
Source:
Sanofi
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05839626
