This is an open-label Phase I/II, first-in-human, multi-center clinical study in sequential cohorts of patients with relapsed or refractory AML or CMML who have exhausted standard treatment options or for whom standard therapy is considered unsuitable. The study is designed to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and to explore anticancer activity of NMS-03592088, a FLT3 (Fms-like tyrosine kinase 3), KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog ) and CSF1R (Colony stimulating factor-1 receptor) inhibitor. The study drug will be administered orally once daily for 21 consecutive days followed by 7 days of rest (each cycle is 28 days, schedule A) or once daily for 28 consecutive days (each cycle is 28 days, schedule B). The study will be conducted in two parts: a Phase I dose escalation and dose expansion part including patients with AML and CMML and a single-stage Phase II exploratory study comprising two parallel cohorts of selected patients that are more likely to respond to the drug: a cohort of AML FLT3 mutated patients and a second one of patients with CMML. Patients previously treated with FLT3 inhibitors are allowed to participate.
The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose, and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).