A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies
Investigating the Safety and Tolerability of an Investigational Medication for Blood-Related Cancers
Study Overview
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
You may be eligible for this study if you meet the following criteria:
- Conditions: Acute Myeloid Leukemia
-
Age: 18 years or above
-
Gender: All
Inclusion Criteria:
- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
Substudy 01:
- Participants must be ≥18 years of age
- Confirmed diagnosis of Acute Myeloid Leukemia
- Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is
defined by the following criteria:
- ≥ 75 years of age, OR
- 18 to 74 years of age and meeting one or more of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
- Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
- Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
- Creatinine clearance ≥30 to <45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
- Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0x upper limit of normal
(ULN).
- Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as
- follows
- Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as
- 0 to 2 for participants ≥75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
- For participants ≥75 years of age, adequate renal function demonstrated by a
creatinine clearance ≥30 mL/min, calculated by modification of diet in renal disease (MDRD)
- Subject with adequate liver function demonstrated by the following:
- For participants 18 to 74 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤3.0 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
- For participants ≥75 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤1.5 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
Exclusion Criteria:
- Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
- Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
- Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease
requiring antiretroviral treatment, or having active hepatitis B or C infection, or
SARS-CoV-2 infection. With exception for:
- HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
- A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
- Active, known, or suspected clinically significant autoimmune disease that has
required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
- Predicted life expectancy ≤3 months.
- Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
- Ongoing adverse event of NCI CTCAE [Version 5.0] Grade 2 or greater severity cause by any prior anti-cancer therapy
Substudy 01:
- Patient with Acute Promyelocytic Leukemia (APL)
- Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
- Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
- Malabsorption syndrome or other condition that precludes enteral route of administration
- A baseline QTc interval of (using the Fridericia correction calculation) >470 msec.
- Subject has received treatment with at least one of the following:
- A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
- Experimental therapies for AML.
- Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
This study investigates the safety and tolerability of an investigational medication combined with other agents in people with certain blood cancers that express a protein called CD123. Hematological malignancies are types of cancer that begin in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. This study is open to both adolescents and adults and includes multiple parts to find the best dose and assess initial effectiveness.
Participants will undergo several procedures, including a screening period to determine eligibility, a treatment period where they receive the investigational medication, and a follow-up period after treatment ends. The study will test different doses to find the most effective and safe amount. Participants will continue the treatment until their disease progresses, they experience serious side effects, or they decide to stop.
- Who can participate: Participants must be 18 years or older with a confirmed diagnosis of Acute Myeloid Leukemia (AML) that expresses CD123 and are not eligible for intensive chemotherapy. Eligibility also includes specific health criteria related to heart, kidney, and liver function.
- Study details: Participants will receive an investigational medication along with other treatments. Type 1 diabetes is a chronic disease where the body's defense system mistakenly attacks specific cells within the pancreas, which make insulin. Insulin helps control sugar in the blood. When these cells are damaged, they cannot make enough insulin. This means people with Type 1 diabetes need to take insulin every day to keep their blood sugar at safe levels.
- Study Timelines: The study will last approximately 2.5 years.