A Phase 1b/2 Open-Label Study of APVO436 in Combination with Venetoclax and Azacitidine in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)

A multi-center, open-label, dose-finding study of five dose levels of APVO436 in
combination with venetoclax and azacitidine (ven/aza) in adult patients with newly
diagnosed, CD123+ AML.

Inclusion Criteria:

- 1. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World
Health Organization (WHO) criteria and not been previously treated.

3. Patients must have CD123-positive AML as confirmed by local flow cytometry (or
immunohistochemistry [IHC]). Confirmation at diagnosis is acceptable.

4. Patient must be considered ineligible for induction therapy defined by at least
one of the following:

1. ≥75 years of age

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3

3. Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection
fraction ≤ 50%, or chronic stable angina)

4. Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)

5. Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet
in Renal Disease (MDRD) formular

6. Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5.
Patient must have a projected life expectancy of ≥12 weeks

Exclusion Criteria:

1. Patient has received treatment with the following:

1. A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML,
myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or
myelodysplastic/myeloproliferative neoplasms (MPS/MPN)

2. CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant
(HSCT)

3. Experimental therapies for MDS or AML

2. Patient is currently participating in another interventional research study.

3. Patient has history of MPN including myelofibrosis, essential thrombocythemia,
polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1
translocation, or AML with BCR-ABL1 translocation.

4. Patient has acute promyelocytic leukemia.

5. Patient has a current autoimmune disorder requiring immunosuppressive therapy such
as systemic (oral or IV) steroid therapy >10 mg methylprednisolone daily or its
equivalent

6. Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any
dose).

7. Patient has known active CNS involvement with AML. Patients who received intrathecal
chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in
this study.

8. Creatinine clearance <30ml/min based on Cockcroft-Gault or MDRD formular.

9. Bilirubin of >3xULN in the absence of Gilbert's Syndrome.

10. AST and/or ALT >3 times the ULN.