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.
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.
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.
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.
Parallel
SAR446523
DrugPharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)
Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A)
The incidence of DLTs will be evaluated using NCI CTCAE version 5.0 criteria.
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.
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
Change from baseline in laboratory abnormalities
Measured as per NCI CTCAE v 5.0.
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.
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.
