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

NCT06634394 | Recruiting Phase 1 FDA Drug

• 1 other identifier: APVO436-5201
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 7

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.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

  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 \[CRS\]).

  Through the end study completion average of 1 year.

Secondary Outcomes (1)

• 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.

Study Arms (1)

Treatment Arm APVO436 in combination with Venetoclax and Azacitidine

EXPERIMENTAL

APVO436 at escalating dose levels in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.

Drug: APVO436; Drug: Venetoclax; Drug: Azacitidine

Interventions

APVO436 DRUG

Infusion drug administered as a 4 hour infusion.

Treatment Arm APVO436 in combination with Venetoclax and Azacitidine

Venetoclax DRUG

Oral tablet given on days 1 through 22, of a 28 day cycle.

Also known as: venclexta

Treatment Arm APVO436 in combination with Venetoclax and Azacitidine

Azacitidine DRUG

Intravenous infusion given on days 1-8 of a 28 day cycle

Also known as: vidaza

Treatment Arm APVO436 in combination with Venetoclax and Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.
• \. Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.
• \. Patient must be considered ineligible for induction therapy defined by at least one of the following:
• ≥75 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
• Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
• Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
• Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks

You may not qualify if:

• Patient has received treatment with the following:
• A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
• CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
• Experimental therapies for MDS or AML
• Patient is currently participating in another interventional research study.
• 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.
• Patient has acute promyelocytic leukemia.
• Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
• Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
• 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.
• Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
• Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
• AST and/or ALT \>3 times the ULN.

Sponsors & Collaborators

• Aptevo Therapeutics: lead

Study Sites (7)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

University of Miami

Miami, Florida, 33124, United States

RECRUITING

University of Kansas

Fairway, Kansas, 66205, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

Oncology Hematology Care

Cincinnati, Ohio, 45226, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Dirk Huebner, MD

  Aptevo Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Caroline Taromino

CONTACT

7735749572; tarominoC@apvo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 9, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 11, 2025

Record last verified: 2024-10

Locations

US (7)