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

A First-in-human, Open-label, Phase 1 Study to Evaluate the Safety, Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of Subcutaneous SAR446523, an Anti-GPRC5D ADCC-enhanced Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Plasma Cell Myeloma Refractory
• Intervention / Treatment: Drug: SAR446523

Detailed Description

The study will be considered ongoing until the last participant last visit has occurred. Participants will be allowed to continue therapy until disease progression, unacceptable AEs, participant or Investigator's request to discontinue treatment.

• Study Type: Interventional
• Enrollment (Estimated): 87
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Investigational Site Number : 0360001
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • Recruiting
      • Investigational Site Number : 0360002
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L3
      • Recruiting
      • Investigational Site Number : 1240005
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Investigational Site Number : 1240001
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Investigational Site Number : 1240002
• France
  • Lille, France, 59037
    • Recruiting
    • Investigational Site Number : 2500002
  • Nantes, France, 44093
    • Recruiting
    • Investigational Site Number : 2500001
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Investigational Site Number : 3760004
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Investigational Site Number : 3760002
  • Malopolskie
    • Tel Aviv, Malopolskie, Israel, 6423906
      • Recruiting
      • Investigational Site Number : 3760001
• Italy
  • Ancona
    • Torette, Ancona, Italy, 60020
      • Recruiting
      • Investigational Site Number : 3800002
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Investigational Site Number : 3800001
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Investigational Site Number : 7240001
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Recruiting
      • Investigational Site Number : 7240002
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic in Arizona - Phoenix- Site Number : 8400005
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida- Site Number : 8400003
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester - Minnesota- Site Number : 8400004
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400001
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital- Site Number : 8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

-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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Dose escalation); Participants will receive SAR446523	Drug: SAR446523; Pharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)
Experimental: Part B Dose-1 (Dose optimization); Participants will receive SAR446523 Dose-1	Drug: SAR446523; Pharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)
Experimental: Part B Dose-2 (Dose optimization); Participants will receive SAR446523 Dose-2	Drug: SAR446523; Pharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Measured as per NCI CTCAE v 5.0	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	Measured as per NCI CTCAE v 5.0.	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)	ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) assessed as per Investigator according to the 2016 International Myeloma Working Group (IMWG) response criteria.	24 months after the Last Participant In (LPI)
VGPR or better rate	VGPR or better rate defined as the proportion of participants with sCR, CR, and VGPR assessed as per Investigator according to the 2016 IMWG response criteria.	24 months after the Last Participant In (LPI)
Clinical benefit rate (CBR)	CBR defined as the rate of participants with confirmed sCR, CR, VGPR, or PR at any time or minimal response (MR) of at least 6 months from the first IMP administration determined per 2016 IMWG response criteria.	24 months after the Last Participant In (LPI)
Duration of response (DoR)	DoR defined as the time from the date of the first response (PR or better) to the date of first documentation of progressive disease (PD) as defined in the 2016 IMWG response criteria, or date of death, whichever occurs first.	24 months after the Last Participant In (LPI)
Time to response (TTR)	TTR defined as the time from the first administration of study IMP to the date of first response (PR or better) that is subsequently confirmed.	24 months after the Last Participant In (LPI)
Progression free survival (PFS)	PFS defined as the time interval from the date of first administration of study IMP to the date of first documentation of PD per 2016 IMWG criteria assessed by study Investigator, or date of death from any cause, whichever comes first.	24 months after the Last Participant In (LPI)
Minimal residual disease (MRD) status negativity	MRD status negative by nextgeneration sequencing (NGS) in bone marrow of participants with a response of CR (or VGPR in case of suspected interference).	24 months after the Last Participant In (LPI)
Number of participants with symptomatic AEs -Part B	The incidence and evaluation of symptomatic AEs from participants' perspective will be measured by using specific items from National Cancer Institute (NCI) patient-reported outcome (PRO) common terminology criteria for adverse events (CTCAE) library.	From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years
Change from baseline in overall side effect bother as measured by the Functional Assessment of Cancer Therapy item 5 (FACT-GP5)- Part B	The FACT GP5 is an assessment focused on the overall side effect impact to inform the tolerability of a treatment. The FACT GP5 ("I am bothered by side effects of treatment") responses are given on a 5 point Likert type scale recalling the past 7 days. Higher scores indicate a higher degree of side effect bother.	From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years
Maximum observed concentration (Cmax)	To characterize the pharmacokinetics (PK) of SAR446523.	Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
First time to reach Cmax (tmax)	To characterize the PK of SAR446523.	Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
Area under the concentration versus time curve calculated from 0 to 168 hours (AUC0-168h)	To characterize the PK of SAR446523.	Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
Proportion of participants with presence of anti-drug antibody (ADA) against SAR446523.	To evaluate potential immunogenicity.	From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• TED18162 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): May 16, 2031
• Study Completion (Estimated): May 16, 2031

Study Registration Dates

• First Submitted: October 3, 2024
• First Submitted That Met QC Criteria: October 7, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: anti-GPRC5D NK cell targeting therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: TED18162; U1111-1301-4016 (Other Identifier: WHO ICTRP); 2024-511667-28 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No