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

NCT05839626 | Terminated Phase 1 DMC

• 3 other identifiers: TCD17710U1111-1279-29852022-502057-33-00
• Study Type: interventional
• Target: 32
• Locations: 7 countries
• Sites: 16

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 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

Conditions

Relapsed/Refractory Multiple Myeloma; Amyloid Light-chain Amyloidosis

Outcome Measures

Primary Outcomes (7)

• 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.

  Cycle 1 - 4 weeks per cycle

• 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

  From Baseline to end of follow-up (approx. 15 months)

• 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.

  Cycles 1 to 4 - 4 weeks per cycle

• Dose escalation (part 1b - RRLCA) Presence of dose limiting toxicities (DLT) at cycle 1

  Cycle 1 - 4 weeks per cycle

• Dose escalation (part 1b - RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

  From baseline to end of follow-up (approx. 15 months)

• Dose expansion (part 3 - 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.

  Cycles 1 to 4 - 4 weeks per cycle

• Dose expansion (part 3-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.

  Cycles 1 to 4 - 4 weeks per cycle

Secondary Outcomes (27)

• Dose escalation (part 1 - RRMM) Overall response rate (ORR)

  Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)

• Dose optimization (part 2 - RRMM) Presence of dose limiting toxicities (DLT)

  Cycles 1 to 4 - 4 weeks per cycle

• Dose optimization (part 2 - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

  From first dose of study treatment up to 30 days after last dose of study treatment (approx. 1 year with cycle of 28 days)

• Dose optimization & expansion (Part 2 & Part 3a - RRMM) Very Good Partial Response (VGPR) or Better Rate

  Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)

• Dose optimization & expansion (Part 2 & Part 3a - RRMM) Duration of response (DOR)

  Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)

Study Arms (6)

SAR445514 RRMM Dose escalation phase (Part 1a)

EXPERIMENTAL

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

Drug: SAR445514

SAR445514 RRLCA Dose escalation phase (part 1b)

EXPERIMENTAL

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

Drug: SAR445514

SAR445514 Dose level A (part 2)

EXPERIMENTAL

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

Drug: SAR445514

SAR445514 Dose level B (part 2)

EXPERIMENTAL

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

Drug: SAR445514

SAR445514 RRMM Dose expansion (part 3a)

EXPERIMENTAL

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

Drug: SAR445514

SAR445514 RRLCA Dose expansion (part 3b)

EXPERIMENTAL

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

Drug: SAR445514

Interventions

SAR445514 DRUG

Powder for solution for injection. Sub Cutaneous administration.

SAR445514 Dose level A (part 2); SAR445514 Dose level B (part 2); SAR445514 RRLCA Dose escalation phase (part 1b); SAR445514 RRLCA Dose expansion (part 3b); SAR445514 RRMM Dose escalation phase (Part 1a); SAR445514 RRMM Dose expansion (part 3a)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (16)

Investigational Site Number : 0360001

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360002

Richmond, Victoria, 3121, Australia

Location

Institut Jules Bordet_Site Number : 0560002

Anderlecht, 1070, Belgium

Location

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

Antwerp, 2020, Belgium

Location

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

Antwerp, 2030, Belgium

Location

Investigational Site Number : 0560001

Antwerp, 2060, Belgium

Location

Investigational Site Number : 2030002

Brno, 625 00, Czechia

Location

Investigational Site Number : 2030001

Ostrava, 708 52, Czechia

Location

Investigational Site Number : 3480001

Budapest, 1085, Hungary

Location

Investigational Site Number : 3800001

Rozzano, Lombardy, 20089, Italy

Location

Hospital Universitario Marqués de Valdecilla_Site Number : 7240001

Santander, Cantabria, 39008, Spain

Location

Institut Catala d´oncologia - Badalona_Site Number : 7240002

Badalona, Catalonia, 08916, Spain

Location

HOSPITAL CLINIC i PROVINCIAL BARCELONA_Site Number : 7240003

Barcelona, 08036, Spain

Location

Investigational Site Number : 8260003

Birmingham, B15 2TH, United Kingdom

Location

Investigational Site Number : 8260002

London, NW1 2BU, United Kingdom

Location

Investigational Site Number : 8260001

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: May 3, 2023
• Study Start: May 15, 2023
• Primary Completion: May 26, 2025
• Study Completion: May 26, 2025
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (4); AU (2); IT (1); ES (3); GB (3); CZ (2); HU (1)