Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML

Inclusion Criteria:

• • Histologically confirmed diagnosis of acute myeloid leukemia (AML) according per 2016 World Health Organization (WHO) criteria.

• Cluster of differentiation marker (CD)33 and CD123 / interleukin (IL)3RAexpression on the subject's blasts, determined by standard Flow AML MRD assay.

• Age ≥ 12

• Relapsed or refractory after one cycle of prior therapy (cytoreductive agentssuch as hydroxyurea, cyclophosphamide, or a single dose of gemtuzumabozogamicin are not considered prior treatment regimens).

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• Adequate baseline organ function, including cardiac, renal, and hepaticfunction as defined by:

• Left ventricular ejection fraction (LVEF) ≥ 50% by multi-gated acquisitionscan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 daysprior to the start of therapy

• No clinically significant abnormalities on a 12-lead electrocardiogram (ECG)

• Creatinine Clearance (CrCl) ≥ 60mL/min

• Serum albumin ≥ 3.2 g/dL (note that albumin infusions are not permitted inorder to enable eligibility)

• Total bilirubin ≤ 1.5 mg/dL

• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 timesthe upper limit of normal (ULN)

• white blood cell (WBC) < 20,000/uL on day of first therapy, cytoreduction maybe achieved using hydroxyurea.

• Ability to understand and willingness to sign a written informed consentdocument.

• Able to adhere to study visit schedule and other protocol requirementsincluding follow up for survival assessment.

• If the patient is a woman of child-bearing potential (WOCBP), they should havea negative serum or urine pregnancy test within 1 week prior totagraxofusp-erzs treatment. (Note: WOCBP include any female who has experiencedmenarche and who has not undergone successful sterilization (hysterectomy,bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacementtherapy with documented serum follicle stimulating hormone level ≥ 35milli-international units per milliliter (mIU/mL).

• Patients agree to use acceptable contraceptive methods for the duration of timein the study, and to continue to use acceptable contraceptive methods for 1week after the last tagraxofusp-erzs infusion.

• The patient has signed informed consent prior to initiation of anystudy-specific procedures or treatment. The patient is able to adhere to thestudy visit schedule and other protocol requirements.

Exclusion Criteria:

• • Prior treatment with tagraxofusp-erzs.

• Primary resistance to or progression on gemtuzumab. Patients who havepreviously received Gemtuzumab, but whose disease was not resistant or did notprogress on it are eligible.

• Active central nervous system involvement. Patients with a history of centralnervous system involvement that has cleared with prior treatments are eligible.

• Blood or bone marrow transplant within 60 days of screening or active graftversus host disease.

• The patient has persistent clinically significant toxicities Grade ≥ 2 fromprevious therapies, including cytotoxic chemotherapy, targeted therapies,biological therapies, or immunotherapies, not readily controlled by supportivemeasures (excluding alopecia, nausea, and fatigue)

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

• The patient has an active malignancy and/or cancer history that may confoundthe assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/orongoing active malignancy must be discussed with the Sponsor before studyentry. Patients with the following neoplastic diagnoses are eligible:non-melanoma skin cancer, carcinoma in situ, cervical intraepithelialneoplasia, organ-confined prostate cancer with no evidence of progressivedisease.

• The patient has clinically significant cardiovascular disease (e.g.uncontrolled or any New York Heart Association Class 3 or 4 congestive heartfailure, uncontrolled angina, history of myocardial infarction, unstable anginaor stroke within 6 months prior to study entry, uncontrolled hypertension orclinically significant arrhythmias not controlled by medication).

• The patient has uncontrolled, clinically significant pulmonary disease (e.g.chronic obstructive pulmonary disease, pulmonary hypertension) that in theopinion of the Investigator would put the patient at significant risk forpulmonary complications during the study.

• The patient is receiving immunosuppressive therapy - with the exception oflow-dose prednisone (≤10 mg/day) - for treatment or prophylaxis ofgraft-versus-host disease (GVHD). If the patient has been on immunosuppressivetreatment or prophylaxis for GVHD, the treatment(s) must have been discontinuedat least 14 days prior to study treatment and there must be no evidence ofGrade ≥ 2 GVHD.

• The patient has uncontrolled intercurrent illness including, but not limitedto, uncontrolled infection, disseminated intravascular coagulation, orpsychiatric illness/social situations that would limit compliance with studyrequirements.

• The patient is pregnant or breastfeeding.

• The patient has a history of human immunodeficiency virus (HIV) infection,active or chronic Hepatitis B, or Hepatitis C.

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