A Safety Study of SGN-CD123A in Patients With Acute Myeloid Leukemia

The study will examine the safety profile of SGN-CD123A. The study will test increasing doses of SGN-CD123A given every 3 weeks to patients.

This study is designed to evaluate the safety, tolerability, and preliminary estimate of antitumor activity of SGN-CD123A. The study will be conducted in 2 parts: Part A is the dose-escalation portion of the trial, designed to identify the maximum tolerated dose (MTD) of SGN-CD123A Part B is the dose-expansion portion of the trial, designed to evaluate SGN-CD123A in patients with differing CD123 expression levels Dose-escalation in Part A will be conducted using a 3+3 study design. Patients with CD123-detectable AML will be enrolled in cohorts at escalating doses of study drug and will receive up to 2 induction cycles of SGN-CD123A treatment at an assigned dose level in 3-week cycles. After completion of dose-escalation, patients will be enrolled in Part B of the study. Patients enrolled in Part B will receive up to 2 induction cycles of SGN-CD123A treatment at a dose level and frequency determined by results in Part A. For both Part A and Part B, a third induction cycle may be permitted with the approval of the study medical monitor. If a patient achieves a complete remission or complete remission with incomplete hematologic recovery, optional post-remission cycles of SGN-CD123A may be administered.

Acute Myeloid Leukemia, Antibody-Drug Conjugate, CD123 Antigen, Drug Therapy, AML, Leukemia, Myeloid, Acute

Inclusion Criteria: Relapsed/refractory acute myeloid leukemia following at least 2 but no more than 3 prior regimens Patients may be eligible after only 1 previous regimen if in a high risk category Adequate baseline renal and hepatic function Eastern Cooperative Oncology Group Status of 0 or 1 CD123-detectable leukemia Exclusion Criteria: Cerebral/meningeal disease related to underlying malignancy Promyelocytic leukemia History of clinically significant pulmonary fibrosis or documented diffusing capacity of the lung for carbon monoxide <50% predicted Prior hematopoietic stem cell transplant Antileukemia or experimental treatment within 4 weeks of study drug (other than hydroxyurea or 6-mercaptopurine) Cardio or cerebral vascular event within 6 months

Li F, Sutherland MK, Yu C, Walter RB, Westendorf L, Valliere-Douglass J, Pan L, Cronkite A, Sussman D, Klussman K, Ulrich M, Anderson ME, Stone IJ, Zeng W, Jonas M, Lewis TS, Goswami M, Wang SA, Senter PD, Law CL, Feldman EJ, Benjamin DR. Characterization of SGN-CD123A, A Potent CD123-Directed Antibody-Drug Conjugate for Acute Myeloid Leukemia. Mol Cancer Ther. 2018 Feb;17(2):554-564. doi: 10.1158/1535-7163.MCT-17-0742. Epub 2017 Nov 15.