A Study to Investigate the Safety and Efficacy of SAR446523 Injected Subcutaneously in Adult Participants With Relapsed/Refractory Myeloma

NCT06630806 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: TED18162U1111-1301-40162024-511667-28
• Study Type: interventional
• Target: 87
• Locations: 7 countries
• Sites: 19

Brief Summary

This is a first-in-human study of SAR446523 conducted in patients with RRMM. The study consists of two parts: Dose escalation (Part A): In this part, up to several dose levels (DLs) of SAR446523 will be explored to determine the maximum administered dose (MAD), maximum tolerated dose (MTD), and recommended dose range (RDR) of 2 dose regimens which will be tested in the dose optimization part. Dose optimization (Part B): In this part, participants will be randomly assigned in a 1:1 ratio using interactive response technology (IRT) to either one of the chosen dose regimens of SAR446523 (determined from data coming from Part A), to determine the optimal dose as the recommended phase 2 dose (RP2D) of SAR446523.

Conditions

Plasma Cell Myeloma Refractory

Keywords

anti-GPRC5D NK cell targeting therapy

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A)

  The incidence of DLTs will be evaluated using NCI CTCAE version 5.0 criteria.

  Cycle 1 (28 days)

• Overall response rate (ORR) - Dose optimization (Part B)

  ORR is defined as the proportion of participants with sCR, CR, VGPR, and PR assessed as per Investigator according to the 2016 IMWG response criteria.

  24 months after the Last Participant In (LPI)

Secondary Outcomes (15)

• Number of participants with treatment emergent adverse events (TEAEs), injection related reactions (IRRs), injection site reactions (ISRs), serious adverse events (SAEs), adverse event of special interests (AESIs)

  From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years

• Change from baseline in laboratory abnormalities

  From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years

• ORR- Dose escalation (Part A)

  24 months after the Last Participant In (LPI)

• VGPR or better rate

  24 months after the Last Participant In (LPI)

• Clinical benefit rate (CBR)

  24 months after the Last Participant In (LPI)

Study Arms (3)

Part A (Dose escalation)

EXPERIMENTAL

Participants will receive SAR446523

Drug: SAR446523

Part B Dose-1 (Dose optimization)

EXPERIMENTAL

Participants will receive SAR446523 Dose-1

Drug: SAR446523

Part B Dose-2 (Dose optimization)

EXPERIMENTAL

Participants will receive SAR446523 Dose-2

Drug: SAR446523

Interventions

SAR446523 DRUG

Pharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)

Part A (Dose escalation); Part B Dose-1 (Dose optimization); Part B Dose-2 (Dose optimization)

Eligibility Criteria

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

You may qualify if:

• Participants with a documented diagnosis of multiple myeloma (MM) with measurable disease.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Dose escalation (Part A)
• Participants must have received at least 3 prior lines of antimyeloma therapy, and must be either relapsed or refractory to the above therapies, or are intolerant to them.
• Note: In Part A, prior exposure to anti g-protein-coupled receptor, class c, group 5, member d (GPRC5D) therapy and anti B-cell maturation antigen (BCMA) therapy is allowed.
• Dose optimization (Part B)
• Participants must have received at least 3 prior lines of antimyeloma therapy and be either relapsed or refractory to immunomodulator (IMiD), proteasome inhibitor (PI), anti CD38 monoclonal antibody (mAb), and anti BCMA targeting agent or are intolerant to them.
• Note: In Part B, prior exposure to antiGPRC5D therapy is not allowed.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply: Eastern cooperative oncology group performance status (ECOG PS) of 2 or greater.
• Primary systemic and localized amyloid light chain (AL) amyloidosis, active polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, active plasma cell leukemia. Participants with central nervous system involvement or with clinical signs of meningeal involvement of multiple myeloma.
• Systemic antimyeloma treatment within 14 days before the first study treatment administration.
• Prior treatment with natural killer (NK)-cell engaging therapy (such as monoclonal antibody with antibody-dependent cellular cytotoxicity as primary mechanism of action) within 90 days of the first study treatment administration.
• Inadequate organ and marrow function.
• Participants with significant concomitant illness.
• The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (19)

Mayo Clinic in Arizona - Phoenix- Site Number : 8400005

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic in Florida- Site Number : 8400003

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic in Rochester - Minnesota- Site Number : 8400004

Rochester, Minnesota, 55905, United States

RECRUITING

Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400001

Hackensack, New Jersey, 07601, United States

RECRUITING

Thomas Jefferson University Hospital- Site Number : 8400002

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Investigational Site Number : 0360001

Wollongong, New South Wales, 2500, Australia

RECRUITING

Investigational Site Number : 0360002

Melbourne, Victoria, 3065, Australia

RECRUITING

Investigational Site Number : 1240005

Vancouver, British Columbia, V5Z 1L3, Canada

RECRUITING

Investigational Site Number : 1240001

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Investigational Site Number : 1240002

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Investigational Site Number : 2500002

Lille, 59037, France

RECRUITING

Investigational Site Number : 2500001

Nantes, 44093, France

RECRUITING

Investigational Site Number : 3760001

Tel Aviv, Malopolskie, 6423906, Israel

RECRUITING

Investigational Site Number : 3760004

Haifa, 3109601, Israel

RECRUITING

Investigational Site Number : 3760002

Jerusalem, 9112001, Israel

RECRUITING

Investigational Site Number : 3800002

Torette, Ancona, 60020, Italy

RECRUITING

Investigational Site Number : 3800001

Rozzano, Milano, 20089, Italy

RECRUITING

Investigational Site Number : 7240002

Barcelona, Barcelona [Barcelona], 08035, Spain

RECRUITING

Investigational Site Number : 7240001

Madrid, 28040, Spain

RECRUITING

Related Links

• TED18162 Plain Language Results Summary

Central Study Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610; Contact-US@sanofi.com

Study Design

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

Model Details: Study is non-randomized for part A but randomized for part B. Study drug will be assigned in sequential manner in Part A but parallel assignment in Part B.

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: October 8, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): May 16, 2031
• Study Completion (Estimated): May 16, 2031
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (5); IT (2); AU (2); ES (2); IL (3); CA (3); FR (2)