Clinical trial NCT06630806: A Study to Investigate the Safety and Efficacy of SAR446523 Injected Subcutaneously in Adult Participants With Relapsed/Refractory Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Plasma Cell Myeloma Refractory
Keywords: anti-GPRC5D NK cell targeting therapy
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-10-08
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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 6 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A)
timeFrame: Cycle 1 (28 days)
measure: Overall response rate (ORR) - Dose optimization (Part B)
timeFrame: 24 months after the Last Participant In (LPI)
Secondary outcomes:
measure: 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)
timeFrame: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years
measure: Change from baseline in laboratory abnormalities
timeFrame: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years
measure: ORR- Dose escalation (Part A)
timeFrame: 24 months after the Last Participant In (LPI)
measure: VGPR or better rate
timeFrame: 24 months after the Last Participant In (LPI)
measure: Clinical benefit rate (CBR)
timeFrame: 24 months after the Last Participant In (LPI)
measure: Duration of response (DoR)
timeFrame: 24 months after the Last Participant In (LPI)
measure: Time to response (TTR)
timeFrame: 24 months after the Last Participant In (LPI)
measure: Progression free survival (PFS)
timeFrame: 24 months after the Last Participant In (LPI)
measure: Minimal residual disease (MRD) status negativity
timeFrame: 24 months after the Last Participant In (LPI)
measure: Number of participants with symptomatic AEs -Part B
timeFrame: From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years
measure: Change from baseline in overall side effect bother as measured by the Functional Assessment of Cancer Therapy item 5 (FACT-GP5)- Part B
timeFrame: From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years
measure: Maximum observed concentration (Cmax)
timeFrame: Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
measure: First time to reach Cmax (tmax)
timeFrame: Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
measure: Area under the concentration versus time curve calculated from 0 to 168 hours (AUC0-168h)
timeFrame: Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)
measure: Proportion of participants with presence of anti-drug antibody (ADA) against SAR446523.
timeFrame: From Cycle 1 Day 1 to 90 days after the date of the last study treatment administration i.e., approximately 5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital- Site Number : 8400002
state: Pennsylvania
city: Wollongong
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360002
state: Victoria
city: Montreal
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760002
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760001
city: Torette
country: Italy
facility: Investigational Site Number : 3800002
state: Ancona
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800001
state: Milano
Study officials:
References: