Tagraxofusp in Patients With CD123+ or With BPDCN-IPh-like Acute Myeloid Leukemia

Inclusion Criteria:

• The patient has evidence of AML in the peripheral blood and/or bone marrow witheither BPDCN-IF [CD123/CD4/CD56 (+)] or with AML that is CD123+ but negative foreither, or both, CD4 and CD56.

• The patient is ≥18 years old.

• The patient must be refractory to at least one previous line of conventional therapy (either high dose therapy or hypomethylating agents) or relapsed after receivingconventional therapy (a maximum of two previous line of therapy is admitted).

• The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS)of 0 to 2.

• The patient has adequate baseline organ function, including cardiac, renal, andhepatic function:

1. Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normalas measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D)echocardiography(ECHO) within 21 days before start of therapy and no clinicallysignificant abnormalities on a 12-lead electrocardiogram (ECG).

2. Serum creatinine ≤1.5 mg/dL (133 μmol/L).

3. Serum albumin ≥3.2 g/dL (32 g/L) (albumin infusions are not permitted to enableeligibility).

4. Bilirubin ≤1.5 mg/dL (26 μmol/L).

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 timesthe upper limit of normal (ULN).

• If the patient is a woman of childbearing potential (WOCBP), she must have anegative serum or urine pregnancy test at screeningwithin 1 week before treatment.

• The patient has signed informed consent before initiation of any study-specificprocedures or treatment.

• The patient is able to adhere to the study visit schedule and other protocolrequirements, including follow-up for survival assessment.

• The patient (male and female) agrees to use acceptable contraceptive methods for theduration of time on the study and continue to use acceptable contraceptive methodsfor 1 week after the last infusion of tagraxofusp.

Exclusion Criteria:

• The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB subtype M3).

• The patient has persistent clinically significant toxicities of Grade≥2 fromprevious chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests [as mandated in the inclusion criteria]).

• The patient has received treatment with chemotherapy, wide-field radiation, orbiologic therapy within 14 days of study entry.

• The patient has received treatment with an investigational agent within 14 days ofstudy entry.

• The patient has previously received treatment with tagraxofusp.

• The patient has an active malignancy and/or cancer history (excluding antecedentMDS) that may confound the assessment of the study endpoints. Patients with a pastcancer history (within 2 years of entry) with substantial potential for recurrenceand/or ongoing active malignancy will be evaluated on a case by case basis. Patientswith the following neoplastic diagnoses are eligible: non-melanoma skin cancer,carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostatecancer with no evidence of progressive disease.

• The patient has clinically significant cardiovascular disease (eg, uncontrolled orany New York Heart Association Class 3 or 4 congestive heart failure, uncontrolledangina, history of myocardial infarction, unstable angina or stroke within 6 monthsbefore study entry, uncontrolled hypertension or clinically significant arrhythmiasnot controlled by medication).

• The patient has uncontrolled, clinically significant pulmonary disease (eg, chronicobstructive pulmonary disease, pulmonary hypertension) that, in the opinion of theInvestigator, would put the patient at significant risk for pulmonary complicationsduring the study.

• The patient has known active or suspected central nervous system (CNS) leukemia. Ifsuspected, CNS leukemia should be ruled out with relevant imaging and/or examinationof cerebrospinal fluid.

• The patient is receiving immunosuppressive therapy - with the exception of low-doseprednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis forGVHD, the treatment(s) must have been discontinued at least 14 days before studytreatment and there must be no evidence of Grade ≥2 GVHD.

• The patient has uncontrolled intercurrent illness including, but not limited to,uncontrolled infection, disseminated intravascular coagulation, or psychiatricillness/social situations that would limit compliance with study requirements.

• The patient is pregnant or breastfeeding.

• The patient has known positive status for human immunodeficiency virus or active orchronic hepatitis B or hepatitis C (Patients with positive serology for HBV can beenrolled and must receive antiviral prophylaxis - i.e lamivudine or entcavir).

• The patient is oxygen-dependent.

• The patient has any medical condition that, in the opinion of the Investigator,places the patient at an unacceptably high risk for toxicities.

• The patient has AML and requires more than 1 g/day of hydroxyurea (Hydroxyureaispermittedatdoses of ≤1 g/day.)