A Safety Study of SGN-CD33A in AML Patients

Overview

This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) administered as a single agent and in combination with a hypomethylating agent (HMA). The main purpose of the study is to find the maximum tolerated dose (MTD, which is the highest dose that does not cause unacceptable side effects) of SGN-CD33A in patients with acute myeloid leukemia (AML). The MTD will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemia activity of SGN-CD33A will be assessed.

This study will explore SGN-CD33A as a monotherapy and in combination with a hypomethylating agent (HMA; i.e., azacitidine or decitabine). Initial study treatment with SGN-CD33A includes a maximum of 2 cycles of treatment for monotherapy and 4 cycles for combination cohorts. Patients who achieve documented CR or CRi (Monotherapy) or clinical benefit (Combination) during the first part of the study are eligible to continue treatment. Additional monotherapy cohorts may include patients with relapsed acute promyelocytic leukemia, relapsed patients with nucleophosmin-1 gene mutation (absence of fms-like tyrosine kinase 3 mutation) (NPM1-mutated, FLT-3 wild type), alternate dosing schedules (fractionated dosing on Days 1 and 4), treatment naive patients with AML who declined intensive therapy, and patients who have relapsed after post-allogeneic stem cell transplant. Patients in the combination cohort will be treated with azacitidine or decitabine per institutional practice prior to SGN-CD33A dosing. Expansion cohorts may be added for further evaluation of safety, pharmacokinetics, pharmacodynamics, and antitumor activity.