This is an open-label, multicenter, Phase 1/Phase 2, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity of SAR443579 in various hematological malignancies.
Study duration per participant is 2.5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
101
Powder for solution for infusion; by IV infusion
City of Hope-Site Number:8400002
Duarte, California, United States
Emory University School of Medicine- Grady Campus- Site Number : 8400006
Atlanta, Georgia, United States
Beth Israel Deaconess Medical Center-Site Number:8400004
Boston, Massachusetts, United States
Weill Cornell Medical College-Site Number:8400003
New York, New York, United States
Montefiore Hutchinson Campus- Site Number : 8400012
The Bronx, New York, United States
The Ohio State University- Site Number : 8400009
Columbus, Ohio, United States
Oregon Health and Science University-Site Number:8400011
Portland, Oregon, United States
The Children's Hospital of Philadelphia- Site Number : 8400013
Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center-Site Number:8400001
Houston, Texas, United States
Seattle Children's Hospital- Site Number : 8400014
Seattle, Washington, United States
...and 13 more locations
Escalation Part: Incidence of dose-limiting toxicity (DLT)
DLTs encompass both hematologic and nonhematologic toxicities, prespecified adverse reactions observed post-administration of SAR443579 and assessed by both the investigator and the sponsor.
Time frame: Day 1 to Day 28
Japan Cohort C: Incidence of DLT in Japanese participants
DLTs encompass both hematologic and nonhematologic toxicities, prespecified adverse reactions observed post-administration of SAR443579 and assessed by both the investigator and the sponsor.
Time frame: Day 1 to Day 28
Expansion/Optimization part (Cohorts A1, A2 & D), AML: Proportion of participants who have a CR + CRh + CRi according to the modified AML IWG 2003 criteria
Measure of clinical response to treatment: Proportion of participants who have a complete remission (CR) + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) according to the modified acute myeloid leukemia (AML) IWG 2003 criteria.
Time frame: Up to 6 months
Expansion/Optimization part (Cohort B), MDS: Overall response rate (CR + CR equivalent + PR + CRL + CRh + HI) according to the IWG 2023 MDS response criteria
Measure of clinical response to treatment: Overall response rate (CR + CR equivalent + partial remission (PR) + CR with limited count recovery (CRL) + CRh + hematologic improvement (HI)) according to the International Working Group (IWG) 2023 myelodysplasia (MDS) response criteria.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A, B and D: Recommended dose for expansion (RDE)
Recommended dose for expansion (RDE) of SAR443579.
Time frame: Up to 12 months
Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Number of participants with TEAEs
Number of participants with treatment-emergent adverse events (TEAEs).
Time frame: Up to 30 months
Cohorts A, B, C and D: Ctrough at Cycle 1
Concentration observed just before treatment administration during repeated dosing (Ctrough).
Time frame: Cycle 1 from Day 1 to Day 28
Cohorts A, B, C and D: Incidence of ADA
Percentage of participants with anti-drug antibody (ADA) against SAR443579.
Time frame: Up to 30 months
Escalation and Expansion/Optimization parts - Japan Cohort C, AML: Rate of CR + CRh + CRi per AML 2003 modified IWG response criteria
Measure of clinical response to treatment.
Time frame: Up to 6 months
Escalation and expansion/Optimization parts - Japan Cohort C, MDS: CR rate and ORR rate per IWG 2023 MDS response criteria for escalation part and ORR rate per IWG 2023
Measure of clinical response to treatment.
Time frame: Up to 6 months
Escalation and Expansion/Optimization parts - Japan Cohort C, B-ALL: Rate of CR + CRh + CRi as defined by National Comprehensive Cancer Network (NCCN)
Measure of clinical response to treatment.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A and D: Overall response rate (ORR)
Measure of clinical response to treatment.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A and D: Duration of CR + CRh + CRi (Duration of CRc)
Measure the length of clinical response to treatment.
Time frame: Up to 30 months
Expansion/Optimization part - Cohorts A and D: Duration of CR + CRi + CRh + PR + MLFS (Duration of overall response rate)
Measure the length of clinical response to treatment.
Time frame: Up to 30 months
Expansion/Optimization part - Cohorts A and D: Alternative CR rate
Measure of clinical response to treatment.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A and D: Duration of CR + CRh (Duration of alternative CR)
Measure the length of clinical response to treatment.
Time frame: Up to 30 months
Expansion/Optimization part - Cohorts A and D: Event-free survival (EFS)
EFS is defined as the time interval from the first day of treatment assignment to the date of earliest evidence of relapse, treatment failure, or death.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A and D: Overall survival (OS)
OS is defined as time interval from the first day of treatment assignment to death from any cause.
Time frame: Up to 30 months
Expansion/Optimization part - Cohorts A and D: Rate of hematopoietic stem cell transplantation (HSCT)
Rate of HSCT procedures immediately following study treatment administration but prior to subsequent therapy for treatment of AML.
Time frame: Up to 30 months
Expansion/Optimization part - Cohorts A and D: Time to treatment failure (TTF)
TTF is defined as the time from first day of treatment assignment to discontinuation for any reason excluding remission, eg, relapsed disease, refractory disease, unacceptable AE, participant preference or death.
Time frame: Up to 6 months
Expansion/Optimization part - Cohorts A and D: Rate of conversion from transfusion dependence
Rate of conversion from transfusion dependence during 56-day post-baseline period.
Time frame: Day 0 to Day 56
Expansion/Optimization part - Cohorts A and D: Rate of participants who are transfusion independent at baseline and remain independent during 56-day postbaseline period
Rate of participants who are transfusion independent at baseline and remain independent during 56-day postbaseline period.
Time frame: Day 0 to Day 56
Expansion/Optimization part - Cohort B: Alternative CR rate
Alternative CR rate defined as proportion of participants with CR, CR equivalent, CRuni, CRbi, and CRh.
Time frame: Up to 6 months
Expansion/Optimization part - Cohort B: Duration of ORR
The time interval from the first documented evidence of CR, CR equivalent, CRL, CRh, PR or HI to PD or relapse from CR, CR equivalent, CRL, CRh, PR or HI as per 2023 IWG recommendations or death due to any cause, whichever comes first.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Event-free survival (EFS)
EFS is defined as the time interval from the first day of treatment assignment to the date of protocol specified events.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Overall survival (OS)
OS is defined as time interval from the first day of treatment assignment to death from any cause.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Rate of hematopoietic stem cell transplantation (HSCT)
Rate of HSCT procedures immediately following study treatment administration but prior to subsequent therapy.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Time to treatment failure (TTF)
TTF is defined as the time interval from first day of treatment assignment to discontinuation for any reason excluding remission, eg, relapsed disease, disease progression, unacceptable AE, participant preference or death.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Duration of alternative CR (CR + CR equivalent + CRL + CRh)
Measure the length of clinical response to treatment.
Time frame: Up to 30 months
Expansion/Optimization part - Cohort B: Progression free survival (PFS)
The time interval from the first day of treatment assignment to the date of PD, relapse from CR (or CR equivalent), PR, CRL, CRh, or HI, death due to any cause, whichever comes first.
Time frame: Up to 30 months
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