Brief Summary
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: dosethe amount of medication taken 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 screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer 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).
Intervention / Treatment
- Biological: SAR443579
- Drug: venetoclax
- Drug: azacitidine
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 diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Acutenew, recent, comes with an urgent or significant sense, is sudden, sharp Myeloid Leukemia
- Ineligible for intensive chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells. Ineligible for intensive chemotherapy is defined by the following criteria:
A) ≥ 75 years of age, OR
B) 18 to 74 years of age and meeting one or more of the following:
- Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer 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 imagingtests that create detailed images of areas inside the body.
- 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:
a) 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.