APVO436 is an experimental therapy being developed by Aptevo Therapeutics to treat acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS).

A man-made antibody, APVO436 helps the body’s T-cells to target cancer cells in AML and kill them.

How does APVO436 work?

CD123 is an adaptor protein that is normally present at low levels on some types of blood cells. Many types of blood cancer produce large quantities of this protein, which makes it an attractive target for immunotherapies.

Normal antibodies recognize a single target and have an adaptor region that is recognized by immune cells. APVO436 is a type of laboratory-made antibody that has two head-groups: one that recognizes CD123 and one that recognizes CD3. CD3 is a receptor protein found on the surface of T-cells. T-cells are a type of immune cell that are responsible for killing infected cells and cancer cells.

By binding to both CD123 and CD3, APVO436 activates the T-cells to specifically recognize and destroy cancer cells expressing CD123.

In pre-clinical studies, treatment with APVO436 was able to significantly reduce tumor volume. The safety and tolerability of the treatment also were evaluated in a primate model.

APVO436 in clinical trials

A Phase 1/1b, open-label, multi-center, dose-escalation clinical trial (NCT03647800) is currently recruiting people with AML or MDS in the U.S. The study will evaluate the safety, pharmacokinetics (movement in the body), pharmacodynamics (effect on the body), and clinical activity of APVO436.

In the first phase of the trial, 10 groups of patients, with six people per group, will be treated with increasing doses of APVO436 (doses one through eight). Once three people in a group complete their first treatment cycle and dose-limiting toxicities have been evaluated, a second set of three patients in that group begins treatment.

Once these participants have completed the first cycle of dosing, and dose-limiting toxicities have been evaluated, the next groups of patients will be treated.

In the second, expansion phase of the trial, the researchers will further examine the recommended dose from the first phase. The second phase will include two expansion groups, consisting of 24 patients with AML and 24 with MDS.

The participants will receive APVO436 in their bloodstream weekly for six 28-day cycles, until disease progression, intolerable toxicity, or withdrawal. Patients showing benefit at the end of the sixth cycle may be given six additional cycles of APVO436.

APVO436 also has been chosen for inclusion in the Beat AML Master Clinical Trial, led by the Leukemia & Lymphoma Society. That trial will evaluate APVO436 in a front-line (initial) AML treatment setting.

The Beat AML Master Clinical Trial was launched in October 2016 and is a groundbreaking, collaborative, clinical trial being conducted at leading national cancer centers. It brings together renowned experts and key stakeholders in AML research and development. With support and guidance from the U.S. Food and Drug Administration (FDA), the trial seeks to change the treatment paradigm for AML and accelerate the development of new, targeted therapies using an innovative precision medicine protocol.

Up to 500 newly diagnosed patients, ages 60 or older, will be screened for genetic changes or mutations associated with the disease. This screening process will take up to a week, after which the participants will be assigned to a therapy based on their genetic profile. Patients who do not have a genetic marker for a specific treatment they will receive a broad-acting therapy. Every patient who enters the trial will receive an option for treatment.


Last updated: Jan. 21, 2020


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