PH 1 Study to Evaluate Safety and Tolerability of XmAb14045 in Patients With CD123-expressing Hematologic Malignancies

Inclusion Criteria:

- Diagnosis of 1 of the following diseases:

- Primary or secondary AML (including erythroleukemia and eosinophilic leukemia,
but excluding acute promyelocytic leukemia)

- B-cell ALL

- BPDCN

- CML in blast phase, resistant or intolerant to tyrosine kinase inhibitor therapy

- Patients with relapsed or refractory disease with no available standard therapy

- ECOG performance status 0-2

- Not a candidate for, or refusing treatment with hematopoietic stem cell
transplantation

- Fertile patients must agree to use effective contraception during and for 4 weeks
after completion of study

- Able and willing to complete the entire study

Exclusion Criteria:

- Systemic antineoplastic therapy (including cytotoxic chemotherapy and toxin
immunoconjugates, but excluding hydroxyurea), unconjugated antibody therapy, or
radiotherapy within 2 weeks of the first dose of study treatment, or small molecule
kinase inhibitors within 6 elimination half-lives of the first dose of study
treatment.

- Prior therapy with CD123- or IL-3R-directed immunotherapies, including monospecific
and bsAbs, immunoconjugates, or chimeric antigen receptor- modified T-cell therapy

- Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to
malignant bone marrow involvement)

- Known uncontrolled central nervous system involvement by malignant disease

- Absolute blast count ≥10,000/mm3 or symptoms of leukostasis

- Diagnosis of promyelocytic leukemia

- Aspartate aminotransferase or alanine aminotransferase at screening >3.0 x upper limit
of normal (ULN) unless considered due to leukemic organ involvement

- Bilirubin >1.5 x ULN, unless prior diagnosis and documentation of leukemic organ
involvement, ongoing hemolysis, or Gilbert's syndrome

- Serum creatinine >2.0 x ULN, or estimated creatinine clearance <40mL/min

- History or evidence of a clinically unstable/uncontrollable disorder, condition or
disease other than primary malignancy, that in the opinion of the Investigator would
pose a risk to the patient safety or interfere with the study evaluation

- Evidence of any active, uncontrolled bacterial, viral, parasitic fungal infections
within 1 week of first dose of study drug

- Positive test for human immunodeficiency virus (HIV) -I or -II antibodies, hepatitis B
surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV)
antibody (unless HCV viral load test by PCR is negative). HBcAb positivity will be
allowed if one or more of the following is true: a) HBsAb is present; b) hepatitis B
DNA testing is negative and the patient is receiving hepatitis B reactivation
prophylaxis with entecavir, tenofovir, or lamivudine

- Patient is pregnant or breast feeding, or planning to become pregnant while enrolled
in the study, up to the End of Study visit