Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.

Inclusion criteria

• Male or female aged ≥ 18 years;
• Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):

• With relapsed or refractory disease without established alternative therapy or
• Secondary to MDS treated at least by hypomethylating agent and without established alternative therapy or
• ≥ 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative therapy
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Able to comply with study procedures
• Adequate renal function within 7 days before the inclusion of the patient defined as:

• Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2
• Adequate hepatic function within 7 days before the inclusion of the patient defined as:

• AST and ALT ≤ 1.5 x ULN
• Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

Exclusion criteria

• Participant already enrolled and treated in the study
• Pregnancy, breastfeeding or possibility of becoming pregnant during the study
• Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
• Presence of ≥ CTCAE Grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE, version 4.03).
• Known carriers of HIV antibodies
• Known history of significant liver disease
• Uncontrolled hepatitis B or C infection
• Known active acute or chronic pancreatitis
• History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
• Any factors that could increase the risk of QTc prolongation or risk of arrhythmic events.