MCLA-117 in Acute Myelogenous Leukemia

Study Design : This open label, single arm, multinational, first-in-human study consists of 2 parts. Part 1 consists of dose escalation cohorts and Part 2 is a dose expansion cohort. The study population will include adult AML patients (and all subtypes of AML, except for APL) with relapse or refractory disease and newly diagnosed elderly untreated AML patients with high risk cytogenetics. In addition, very high-risk MDS patients with relapsed or refractory disease are eligible. In Part 1, dose escalations cohorts are followed until dose-limiting toxicity (DLT) or a maximum tolerated dose (MTD) or RecommendedPart2Dose (RP2D) is defined. Dose escalation decisions will be made by the Data Review Committee and will be primarily guided by safety data observed through the end of Cycle 1, as well as on-going assessment of safety beyond Cycle 1 in later cohorts. Part 2 will begin once the MTD or RP2D is determined in Part 1. Part 2 will further characterize the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), immunogenicity and to assess preliminary efficacy of MCLA-117. This part will enroll approximately 30 evaluable patients (defined as evaluable for first efficacy assessment). For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until the last dose of study drug with treatment cycles of 28 days); and a Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 1 year). Participants' safety will be monitored throughout the study. Patients will be permitted to receive MCLA-117 beyond Cycle 1 if conditions allow this. Number of Sites: Approximately 15 centers in five countries are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.