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

Primary Purpose

Relapsed/Refractory Multiple Myeloma, Amyloid Light-chain Amyloidosis

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SAR445514
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, 2a, 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: 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, 2a, 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: N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >8500 ng/mL New York Heart Association (NYHA) classification IIIb or IV heart failure 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) 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 Hospitalization in the last 4 weeks prior to treatment related to a cardiovascular event 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 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 randomization) 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. Participants with a contraindication to dexamethasone Received any other investigational drugs or prohibited therapy for this study within 28 days or 5 half-lives from study treatment, whichever is shorter Hemoglobin <8 g/dL (5.0 mmol/L) Platelets <50 × 10^9/L (not permissible to transfuse a participant within 1 weeks 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 Patients 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 patients recover to Grade 2 or less under anti-hypercalcemia treatment. 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 The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Sites / Locations

  • Investigational Site Number :0360001Recruiting
  • Investigational Site Number :0360002Recruiting
  • Investigational Site Number :0560002Recruiting
  • Investigational Site Number :0560001Recruiting
  • Investigational Site Number :7240003Recruiting
  • Investigational Site Number :7240001Recruiting
  • Investigational Site Number :8260002Recruiting
  • Investigational Site Number :8260001Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

SAR445514 RRMM Dose escalation phase (Part 1a)

SAR445514 RRLCA Dose escalation phase (part 1b)

SAR445514 Dose level A (part 2)

SAR445514 Dose level B (part 2)

SAR445514 RRMM Dose expansion (part 3a)

SAR445514 RRLCA Dose expansion (part 3b)

Arm Description

SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA)) using subcutaneous route (SC)

SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA) using subcutaneous route (SC)

Outcomes

Primary Outcome Measures

Dose escalation (part 1a - RRMM) Presence of dose limiting toxicities (DLT)
DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or ICANS.
Dose escalation (part 1a - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Dose optimization (part 2 - RRMM) Overall response rate (ORR)
ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria, after the last participant is treated for at least 4 cycles or prematurely discontinued.
Dose escalation (part 1b - RRLCA) Presence of dose limiting toxicities (DLT) at cycle 1
Dose escalation (part 1b - RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Dose expansion (part 3a - RRMM) Overall response rate (ORR)
ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria.
Dose expansion (part 3b-RRLCA) Hematological response (HR)
HR is defined as the proportion of participants with sCR, CR, VGPR, and PR according to the European society of hematology/International society of hematology working group guidelines.

Secondary Outcome Measures

Dose escalation (part 1a - RRMM) Overall response rate (ORR)
ORR defined as the proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria.
Dose optimization (part 2 - RRMM) Presence of dose limiting toxicities (DLT)
Dose optimization (part 2 - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Very Good Partial Response (VGPR) or Better Rate
VGPR is defined as the proportion of participants with sCR, CR, and VGPR according to the 2016 IMWG criteria.
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Duration of response (DOR)
DOR is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better).
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Time to first response (TT1R)
TT1R is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better).
Dose optimization & expansion (Part 2 & Part 3a -RRMM) Time to best response (TTBR)
TTBR is defined as the time from the first administration of the IMP to the date of first occurrence of best overall response (PR or better) that is subsequently confirmed.
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Progression free survival (PFS)
PFS is defined as the time from the date of the first administration of the IMP to the date of first documentation of progressive disease or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments.
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Overall survival (OS)
OS is defined as the time from the date of the first administration of the IMP to death from any cause.
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Clinical benefit rate (CBR)
CBR is the rate of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months from the first IMP administration determined by the Investigator per IMWG 2016 criteria.
Dose escalation (part 1b - RRLCA) Overall Hematological Response (OHR)
OHR is defined as the proportion of participants with CR, VGPR, and PR according to the International Society of Amyloidosis guidelines (ISA 2012).
Dose extension (part 3b - RRLCA) Hematological complete response rate (HCR).
HCR is defined as the proportion of patients with complete response according to the ISA 2012.
Dose expansion (part 3b - RRLCA) Overall survival (OS)
OS is defined as the time from the date of study entry to death from any cause.
Dose expansion (part 3b - RRLCA) Progression-Free Survival (PFS).
PFS is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause.
Dose expansion (part 3b - RRLCA) Time to first hematological response (TT1HR)
TT1HR is defined as the time from the first administration of the IMP to the date of first hematological response (PR or better) that is subsequently confirmed.
Dose expansion (part 3b - RRLCA) Duration of hematological response (DOHR)
DOHR is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause.
Dose expansion (Part 3 - RRMM & RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
Incidence rate of infusion associated reactions (IARs)
Incidence rate of injection site reactions (ISR)
Incidence of laboratory abnormalities
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: AUClast
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast)
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: Cmax
Maximum observed concentration
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: Tmax
First time to reach Cmax
Incidence of anti-drug antibody (ADA) against SAR445514 in monotherapy
Dose extension (Part 3 - RRMM & RRLCA) Minimum Residual Disease (MRD) negativity rate
MRD status in patients with response of VGPR or better

Full Information

First Posted
March 31, 2023
Last Updated
September 22, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05839626
Brief 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)
Official Title
First-in-human, Open-label Phase 1/2 Study to Investigate Safety and Efficacy of SAR445514, an NKcell Engager (NKCE) Targeting B-cell Maturation Antigen (BCMA) in Monotherapy in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and in Relapsed/Refractory Light-chain Amyloidosis (RRLCA)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2023 (Actual)
Primary Completion Date
January 3, 2026 (Anticipated)
Study Completion Date
March 16, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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 the confirmed recommended Phase 2 dose (cRP2D) and schedule for SAR445514 in RRMM (Part 3a) and RRLCA (Part 3b). Approximately 101 participants will be enrolled and treated by study intervention and separated as such: Part 1a: Approximately 18 to 30 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Multiple Myeloma, Amyloid Light-chain Amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
101 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SAR445514 RRMM Dose escalation phase (Part 1a)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)
Arm Title
SAR445514 RRLCA Dose escalation phase (part 1b)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA)) using subcutaneous route (SC)
Arm Title
SAR445514 Dose level A (part 2)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)
Arm Title
SAR445514 Dose level B (part 2)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)
Arm Title
SAR445514 RRMM Dose expansion (part 3a)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)
Arm Title
SAR445514 RRLCA Dose expansion (part 3b)
Arm Type
Experimental
Arm Description
SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA) using subcutaneous route (SC)
Intervention Type
Drug
Intervention Name(s)
SAR445514
Intervention Description
Powder for solution for injection. Sub Cutaneous administration.
Primary Outcome Measure Information:
Title
Dose escalation (part 1a - RRMM) Presence of dose limiting toxicities (DLT)
Description
DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or ICANS.
Time Frame
Cycle 1 - 4 weeks per cycle
Title
Dose escalation (part 1a - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Description
Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time Frame
From Baseline to end of follow-up (approx. 15 months)
Title
Dose optimization (part 2 - RRMM) Overall response rate (ORR)
Description
ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria, after the last participant is treated for at least 4 cycles or prematurely discontinued.
Time Frame
Cycles 1 to 4 - 4 weeks per cycle
Title
Dose escalation (part 1b - RRLCA) Presence of dose limiting toxicities (DLT) at cycle 1
Time Frame
Cycle 1 - 4 weeks per cycle
Title
Dose escalation (part 1b - RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Time Frame
From baseline to end of follow-up (approx. 15 months)
Title
Dose expansion (part 3a - RRMM) Overall response rate (ORR)
Description
ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria.
Time Frame
Cycles 1 to 4 - 4 weeks per cycle
Title
Dose expansion (part 3b-RRLCA) Hematological response (HR)
Description
HR is defined as the proportion of participants with sCR, CR, VGPR, and PR according to the European society of hematology/International society of hematology working group guidelines.
Time Frame
Cycles 1 to 4 - 4 weeks per cycle
Secondary Outcome Measure Information:
Title
Dose escalation (part 1a - RRMM) Overall response rate (ORR)
Description
ORR defined as the proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose optimization (part 2 - RRMM) Presence of dose limiting toxicities (DLT)
Time Frame
Cycles 1 to 4 - 4 weeks per cycle
Title
Dose optimization (part 2 - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Description
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
Time Frame
From first dose of study treatment up to 30 days after last dose of study treatment (approx. 1 year with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Very Good Partial Response (VGPR) or Better Rate
Description
VGPR is defined as the proportion of participants with sCR, CR, and VGPR according to the 2016 IMWG criteria.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Duration of response (DOR)
Description
DOR is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better).
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Time to first response (TT1R)
Description
TT1R is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better).
Time Frame
Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a -RRMM) Time to best response (TTBR)
Description
TTBR is defined as the time from the first administration of the IMP to the date of first occurrence of best overall response (PR or better) that is subsequently confirmed.
Time Frame
Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Progression free survival (PFS)
Description
PFS is defined as the time from the date of the first administration of the IMP to the date of first documentation of progressive disease or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Overall survival (OS)
Description
OS is defined as the time from the date of the first administration of the IMP to death from any cause.
Time Frame
Cycle 1 to end of follow-up or death (approx. 15 months with cycle of 28 days)
Title
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Clinical benefit rate (CBR)
Description
CBR is the rate of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months from the first IMP administration determined by the Investigator per IMWG 2016 criteria.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose escalation (part 1b - RRLCA) Overall Hematological Response (OHR)
Description
OHR is defined as the proportion of participants with CR, VGPR, and PR according to the International Society of Amyloidosis guidelines (ISA 2012).
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose extension (part 3b - RRLCA) Hematological complete response rate (HCR).
Description
HCR is defined as the proportion of patients with complete response according to the ISA 2012.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose expansion (part 3b - RRLCA) Overall survival (OS)
Description
OS is defined as the time from the date of study entry to death from any cause.
Time Frame
Cycle 1 to death or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose expansion (part 3b - RRLCA) Progression-Free Survival (PFS).
Description
PFS is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause.
Time Frame
Cycle 1 to first progressive disease (organ or hematological) or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose expansion (part 3b - RRLCA) Time to first hematological response (TT1HR)
Description
TT1HR is defined as the time from the first administration of the IMP to the date of first hematological response (PR or better) that is subsequently confirmed.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose expansion (part 3b - RRLCA) Duration of hematological response (DOHR)
Description
DOHR is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause.
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Title
Dose expansion (Part 3 - RRMM & RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Description
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
Time Frame
From first dose of study treatment up to 30 days after last dose of study treatment (approx. 15 months with cycle of 28 days)
Title
Incidence rate of infusion associated reactions (IARs)
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Incidence rate of injection site reactions (ISR)
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Incidence of laboratory abnormalities
Time Frame
From cycle 1 to end of follow-up (approx. of 15 months with cycle of 28 days)
Title
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: AUClast
Description
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast)
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: Cmax
Description
Maximum observed concentration
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Assessment of pharmacokinetics (PK) parameters of SAR445514 in monotherapy: Tmax
Description
First time to reach Cmax
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Incidence of anti-drug antibody (ADA) against SAR445514 in monotherapy
Time Frame
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Title
Dose extension (Part 3 - RRMM & RRLCA) Minimum Residual Disease (MRD) negativity rate
Description
MRD status in patients with response of VGPR or better
Time Frame
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 2a, 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: 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, 2a, 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: N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >8500 ng/mL New York Heart Association (NYHA) classification IIIb or IV heart failure 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) 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 Hospitalization in the last 4 weeks prior to treatment related to a cardiovascular event 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 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 randomization) 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. Participants with a contraindication to dexamethasone Received any other investigational drugs or prohibited therapy for this study within 28 days or 5 half-lives from study treatment, whichever is shorter Hemoglobin <8 g/dL (5.0 mmol/L) Platelets <50 × 10^9/L (not permissible to transfuse a participant within 1 weeks 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 Patients 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 patients recover to Grade 2 or less under anti-hypercalcemia treatment. 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 The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
contact-us@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :0360001
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0360002
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0560002
City
Anderlecht
ZIP/Postal Code
1070
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0560001
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240003
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240001
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260002
City
London
ZIP/Postal Code
WC1N3BG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260001
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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