APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia (AML)
• Interventions: Drug: APVO436; Drug: Venetoclax; Drug: Azacitidine

• Registration Number: NCT06634394
• Lead Sponsor: Aptevo Therapeutics

Brief Summary

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.

Detailed Description

Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. In Cycle 1 (C1) only, to reduce the risk of CRS, each cohort will receive 4 priming doses of APVO436 respectively. APVO436 will be given in combination with venetoclax and azacitidine. For C1D15 and all doses in each subsequent cycle, cohorts will receive APVO436 at the determined cohort dose level.

APVO436 dosing will be administered by a 4-hour intravenous (IV) infusion.

Study Timeline

• Status Verified: 2024-10
• Study Start: 2024-10-01
• Study First Submitted: 2024-10-04
• Study First Submitted QC: 2024-10-08
• Study First Posted: 2024-10-09
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-11
• Primary Completion: 2027-10
• Study Completion: 2028-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

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.

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

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

  4. ≥75 years of age

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

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

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

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

  9. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm APVO436 in combination with Venetoclax and Azacitidine	APVO436	APVO436 at escalating dose levels in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Treatment Arm APVO436 in combination with Venetoclax and Azacitidine	Venetoclax	APVO436 at escalating dose levels in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Treatment Arm APVO436 in combination with Venetoclax and Azacitidine	Azacitidine	APVO436 at escalating dose levels in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.

Primary Outcome Measures

Name	Time	Method
To assess the safety, tolerability, and maximum tolerated dose (MTD) of increasing doses of APVO436 in combination with venetoclax/azacitidine in patients with newly diagnosed AML	Through the end study completion average of 1 year.	Incidence and severity of treatment emergent adverse events (TEAEs), including ≥Grade 3 adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs: ≥Grade 2 infusion related reaction (IRR), ≥Grade 2 cardiac toxicity, and ≥Grade 2 neurotoxicity as complication of cytokine release syndrome \[CRS\]).

Secondary Outcome Measures

Name	Time	Method
Determine the efficacy of increasing doses of APVO436 in combination with venetoclax and azacitidine in patients with newly diagnosed AML	Through the end study completion average of 1 year.	Complete remission (CR) rate

Trial Locations

Locations (7)

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

University of Miami; 🇺🇸 Miami, Florida, United States

University of Kansas; 🇺🇸 Fairway, Kansas, United States

Gabrail Cancer Center; 🇺🇸 Canton, Ohio, United States

Oncology Hematology Care; 🇺🇸 Cincinnati,, Ohio, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States