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A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies
This is a parallel, Phase 1/Phase 2, randomized, open label, multi-cohort, multi-center study assessing the safety, tolerability and preliminary efficacy of SAR443579 with different agents for treatment in adolescent and/or adult participants with CD123 expressing hematological malignancies. This protocol is structured as a master protocol (containing common protocol elements). Individual sub-studies will explore SAR443579 with combination partners, which may include approved or investigational agents.
Experimental sub-studies will be tested through 3 parts: Part 1: dose finding (such as dose escalation/ safety run-in). Part 2: dose optimization (when applicable). Part 3: dose expansion.
In each sub-study, a dose escalation will identify preliminary recommended dose for expansion (pRDE) of SAR443579 and its respective combination partner. Following the determination of the preliminary RDE, additional participants will be enrolled in the dose expansion part, or if dose optimization needs to be further evaluated, additional participants will be enrolled in the "dose optimization/expansion" part. Dose optimization and dose expansion part could involve randomization depending on specific sub-study design.
Study will consist of a screening period, treatment period, and follow-up period. Participants will receive study treatment until documented disease progression, unacceptable adverse events, participant's decision to stop study treatment, or completion of the maximum cycles allowed in the sub-studies, or the participant meets other criteria for discontinuation per study protocol (whichever occurs first).
Study details:
Substudy 01:. Title: A Phase 1/Phase 2, open-label, multi-center study, assessing the safety, tolerability and the preliminary efficacy of SAR443579 administered in combination with azacitidine + venetoclax in adult participants with CD123 expressing newly diagnosed Acute Myeloid Leukemia (ND-AML) that are ineligible for intensive chemotherapy. Short title: A study to investigate natural killer cell engager (SAR443579) in combination with azacitidine + venetoclax in adult participants with newly diagnosed acute myeloid leukemia.
The expected duration of the study for a participant is approximately about 2. 5 years. The study duration includes a screening period, an induction and maintenance.
After the end of study treatment participants will enter the follow-up period for up to 2 years. Planned number of participants:. 22 participants planned to be screened, 8 being adults and 14 being elderly; 9-18 participants planned to be enrolled (dose escalation part).
Enrollment will be paused upon completion of Part 1: Dose Escalation. The available data will be reviewed and the recommended doses and schedule for optimization will be selected by the study board. Enrollment in the Part 2: Dose optimization and Part 3: Dose expansion will be provided in a future protocol amendment.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-08-13
Primary completion: 2029-02-12
Study completion finish: 2029-02-12
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT06508489
Intervention or treatment
BIOLOGICAL: SAR443579
DRUG: venetoclax
DRUG: azacitidine
Conditions
- • Acute Myeloid Leukemia
Find a site
Closest Location:
Investigational Site Number : 0360001
Research sites nearby
Select from list below to view details:
Investigational Site Number : 0360001
Melbourne, Victoria, Australia
Investigational Site Number : 0360002
Wollongong, New South Wales, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Substudy 01: SAR443579 + azacitidine + venetoclax
| BIOLOGICAL: SAR443579
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Number of participants with adverse events (AEs)/serious adverse events (SAEs)/adverse events of special interest (AESIs), laboratory abnormalities | Not Specified | Day 1 to 30 days after the last administration of study treatment |
| Substudy 01: Incidence of dose limiting toxicities (DLTs) (escalation part) | Not Specified | Day 1 to Day 28 |
| Substudy 01: Complete Remission (CR) rate (optimization part) | Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML | Day 1 to 30 days after the last administration of study treatment |
| Substudy 01: Complete Remission (CR) rate (expansion part) | Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML | Day 1 up to 6 months |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and clinically significant laboratory abnormalities (expansion part) | According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) | Day 1 to 30 days after the last administration of study treatment |
| Incidence of anti-drug anti body (ADA) against SAR443579 | Not Specified | Day 1 to 30 days after the last administration of study treatment |
| Substudy 01: Percentage of participants with Minimal residual disease (expansion part) | As defined by 2022 ELN recommendations for AML | Day 1 up to 6 months |
| Substudy 01: Pharmacokinetic (PK) parameter of SAR443579: Ctrough | Concentrations observed at the end the dosing period during repeated administration for SAR443579 | Day 1 up to 10 cycles (each cycle 28 days) |
| Substudy 01: PK parameter of venetoclax: Cmax | Maximum concentration observed for venetoclax | Day 1 to Day 28 |
| Substudy 01: PK parameter of azacitidine: Cmax | Maximum concentration observed for azacitidine | Day 1 to Day 28 |
| Substudy 01: PK parameter of venetoclax: AUC | Area under the blood concentration versus time curve extrapolated to infinity for venetoclax | Day 1 to Day 28 |
| Substudy 01: PK parameter of azacitidine: AUC | Area under the blood concentration versus time curve extrapolated to infinity for azacitidine | Day 1 to Day 28 |
| Substudy 01: Composite Complete Remission (CRc) rate | Proportion of participants who have a CR (Complete Remission) + CRh (complete remission with partial hematologic recovery) + CRi (Complete Remission with Incomplete Hematologic Recovery) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML. (CRc = CR + CRh + CRi) | Day 1 up to 6 months |
| Substudy 01: Overall response rate (expansion part) | Proportion of participants who have a CR or CRi or CRh or PR or MLFS (morphological leukemia-free state) according to the 2022 ELN criteria. | Day 1 up to 6 months |
| Substudy 01: Duration of CR (expansion part) | Defined as the time interval from the first documented evidence of CR until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Duration of CRc (expansion part) | Defined as the time interval from first documented evidence of CRc (CR, CRh or CRi) until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Duration of overall response (expansion part) | Defined as the time from the first documented evidence of CR or CRi or CRh or PR or MLFS until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Alternative CR rate (expansion part) | Defined as the proportion of participants with CR+CRh (complete remission with partial hematological recovery) | Day 1 up to 6 months |
| Substudy 01: Duration of alternative CR (expansion part) | Defined as the time from the first documented evidence of CR or CRh until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Event-free survival (EFS) (expansion part) | Defined as the time interval from the first day of treatment assignment to the date of earliest evidence of relapse, treatment failure, or death | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Overall survival (expansion part) | Defined as time interval from the first day of treatment assignment to death from any cause | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Rate of hematopoietic stem cell transplantation (HSCT) procedures immediately following study treatment administration but prior to subsequent therapy for treatment of AML (all parts) | The HSCT rate is defined as the proportion of such participants who undergo HSCT through study treatment but before subsequent therapy, among the safety/exposed population | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Time to treatment failure (TTF) (expansion part) | Defined as the time from first day of treatment assignment to discontinuation for any reason excluding remission, for example relapsed disease, refractory disease, unacceptable AE, participant preference or death | Day 1 up to 24 months after the last administration from study treatment |
| Substudy 01: Rate of conversion from transfusion dependence to transfusion independence (all parts) | The transfusion dependency (TD) at baseline is based on the receipt of any red blood cell or platelets transfusions within at least 28 days prior to the start of study treatment. For post baseline treatment, transfusion independency (TI) will be defined as the absence of transfusion during any 56 consecutive day period during treatment. | Day 1 to Day 56 |
| Substudy 01: Rate of participants who are transfusion independent at baseline and remain independent during 56-day post-baseline period (all parts) | Transfusion independency (TI) will be defined as the absence of transfusion during any 56 consecutive day period during treatment. | Day 1 to Day 56 |
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