Phase I/II Trial of S65487 Plus Azacitidine in Acute Myeloid Leukemia

Prior treatment

• Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery
• Any radiotherapy within 3 weeks before the first IMP administration,
• Treatment with hypomethylating agents (decitabine/azacitidine) or Venetoclax for AHD (antecedent hematologic disorders) in the 3 months prior to the first IMP intake

Other illness

• Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 3, 2019 for Acute Myeloid Leukemia

Lab values

• Allogenic stem cell transplant within 3 months before the first IMP administration and/or participants with active Graft-versus-host disease within 3 months before the first IMP administration and/or participants who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or participant who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration

Other

• Acute promyelocytic leukemia (APL, French-American-British M3 classification)

• Male or female participant aged ≥ 18 years old
• Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes:
  • Previous myelodysplastic syndrome transformed
  • AML due to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 3 years
• Participants not eligible for standard induction chemotherapy
  • Aged ≥ 75 years old
  • Or Age ≥18 years with at least one of the following comorbidities:
  • Clinically significant heart or lung comorbidities, as reflected by at least one of:
  • Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
  • Forced expiratory volume in 1 second (FEV1) ≤65% of expected
  • Other contraindication(s) to anthracycline therapy (must be documented)
  • Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented
• ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG ≤ 2.
• Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol.
• Adequate renal and hepatic function
• Circulating White Blood Cell Count (WBC count) \< 25\*109 G/L (with or without use of hydroxycarbamide/leukapheresis)
• Serum potassium, serum calcium, serum phosphates, serum magnesium within normal limits with or without supplementation.