Study of APVO436 in Patients With AML or MDS
- 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).
- 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
Salt Lake City
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
Aptevo Research and Development LLC
- Primary ID Protocol 5001
- Secondary IDs NCI-2019-00146
- Clinicaltrials.gov ID NCT03647800