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Study of APVO436 in Patients With AML or MDS

Trial Status: Active

APVO436 is being studied in this Phase 1 / 1b, open-label, multi-center, dose-escalation study to evaluate the safety, pharmacokinetic / pharmacodynamic and clinical activity of APVO436 monotherapy in: 1) patients with AML that have relapsed on prior therapy or are refractory to therapy and are not candidates for intensive chemotherapy or transplant, and 2) patients with MDS that have > 5% blasts in the bone marrow or blasts in the peripheral blood who have also failed prior therapy with an hypomethylating agent (HMA). The primary objective of the Phase 1 part of the study is to determine the recommended dose of APVO436 administered intravenously to patients with AML or MDS. The primary objective of the Phase 1b part of the study is to evaluate the clinical activity of APVO436 in patients with AML or MDS.

Inclusion Criteria

  • Signed informed consent. Consent must be obtained prior to any study-related procedure.
  • Age ≥ 18 years
  • Histologically confirmed AML or MDS:
  • AML - relapsed or refractory AML and refuses or is not a candidate for intensive chemotherapy (due to prior failure or not eligible due to expected intolerance) or allogeneic transplant
  • MDS - relapsed or refractory MDS with > 5% blasts in the marrow or any blasts in the peripheral blood. Patients must have failed prior treatment with an HMA (azacitidine, decitabine, or other HMA agent); failure is defined as intolerance to HMA, lack of response [no complete remission (CR) by at least 6 cycles], or have IWG-defined progressive disease during or after treatment with an HMA.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Life expectancy of > 2 months in the Investigator's opinion
  • White blood cells (WBC) ≤ 25,000 cells/mm3 (may receive hydroxyurea to bring WBC count down prior to and during the first cycle of treatment with study drug if necessary)
  • Creatinine ≤ 2 × upper limit of normal (ULN)
  • Adequate liver test parameters: total bilirubin < 2.5 × ULN (if disease related or secondary to Gilbert's disease, then total bilirubin < 3.5 mg/dL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) < 3 × ULN
  • Prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 × ULN
  • Patients and partners of childbearing potential must be willing to use adequate contraception during the study and for 2 months after last study drug administration. Adequate contraception means less than 1% chance of pregnancy may occur with proper use of the method(s).

Exclusion Criteria

  • Any central nervous system (CNS) (cerebral/meningeal) disease related to underlying malignancy
  • History of seizures
  • Acute promyelocytic leukemia
  • Prior anti-CD123 therapy outside of this study
  • Any clinically significant graft-versus-host disease (GVHD) secondary to prior allogenic transplant. Patients must be >90 days from transplant and have been on no immunosuppressive therapy for >30 days. Topical corticosteroids for minor skin rash (<5% body surface area) is acceptable. Prior solid organ transplant is acceptable provided the patient is on no immunosuppressive therapy.
  • Any therapy or experimental treatment for MDS or AML within 7 days of the first dose of study drug. Must have recovered to Grade ≤ 1 from any Grade 2 to 4 toxicity from previous treatment. The use of hydroxyurea is acceptable and does not exclude the patient.
  • Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials are permitted.
  • Major surgery within 3 weeks prior to first dose of study drug
  • Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV)
  • Pregnant or breast feeding
  • Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate cancer that is well controlled with anti-hormonal therapy
  • Any current autoimmune disorder requiring immunosuppressive therapy
  • Requires more than a replacement dose of corticosteroids (i.e., > 10 mg/day of prednisone or equivalent)
  • Any uncontrolled medical condition, including but not limited to:
  • Symptomatic congestive heart failure ≥ Class III (New York Heart Association Functional Classification)
  • Uncontrolled hypertension
  • Unstable angina
  • Myocardial infarction within previous 6 months
  • Clinically significant arrhythmias not controlled by medication
  • Uncontrolled metabolic disorders such as hypercalcemia
  • Substance use disorder, psychiatric, cognitive, or any other condition that, in the opinion of the Investigator, would pose a risk to the patient's safety, may compromise the patient's ability to understand and comply with the protocol or provide informed consent, or interfere with the study evaluation
  • Any difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration, or may cause a safety concern for the patient

California

San Francisco
UCSF Medical Center-Mount Zion
Status: APPROVED
Contact: UCSF Clinical Trials
Phone: 877-827-3222

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Phase 1 - Open-label, Dose Escalation: The dose escalation stage of the study will test step-dose and/or split-dose regimens infused weekly over 10 dose levels (cohorts). Cohorts 1 to 10 will follow a 3 + 3 design. The next cohort is started after patients in the previous dose cohort have completed the first cycle of dosing and an evaluation for dose-limiting toxicities (DLTs) during the first cycle has been completed. Phase 1b - Expansion: The recommended-dose from Phase 1 will be further examined in 2 expansion cohorts consisting 24 AML patients (Cohort 1) and 24 MDS patients (Cohort 2). Patients will receive APVO436 intravenously weekly for six 28-day cycles, unless disease progression, intolerable toxicity, or withdrawal of consent occurs earlier. Patients with evidence of clinical benefit at the end of Cycle 6 in the absence of unacceptable toxicity may also continue on study for up to 12 total cycles at the discretion of Investigator (6 cycles in addition to the initial 6 cycles).

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Aptevo Research and Development LLC

  • Primary ID Protocol 5001
  • Secondary IDs NCI-2019-00146
  • Clinicaltrials.gov ID NCT03647800