APVO436 Combo Yields Favorable Responses in Acute Myeloid Leukemia

APVO436 is a CD3xCD123 agent designed to redirect the immune system to destroy CD123-expressing leukemia cells. It is an antibody-like recombinant protein therapeutic that brings together leukemia cells and T-cells to eliminate cancerous cells.

The bispecific drug candidate APVO436 yielded positive clinical outcomes in combination with venetoclax (Venclexta) and azacitidine among patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), according to a press release from Aptevo Therapeutics on data from a phase 1b dose escalation trial (NCT03647800).

In a group of 11 patients who were naïve to venetoclax therapy, 82% (n = 9) experienced a favorable response to treatment and could be included in the duration of remission (DOR) analysis. Three patients had a response sufficient to receive stem cell transplant, which may provide the “best probability for survival and highest benefit to patients,”according to the press release.

One patient remained on study with a sustained complete response for 8 cycles and a DOR of at least 8 months. The median DOR has not been reached. A substantial number of patients did not experienced a relapse event and either remained on treatment or moved on to receive transplantation.

Two phase 2 trials are planned for the future that are designed to further evaluate this combination in both the first-line and relapsed/refractory settings. Overall, the trials are expected to include a combined total of approximately 100 patients. Interim findings are expected in late 2024.

Previously reported findings from the phase 1b trial include a 91% clinical benefit rate. Additionally, less than 25% of patients experienced cytokine release syndrome (CRS), with most instances being grade 1 or 2 in severity and manageable in the clinic.

APVO436 is a CD3xCD123 agent designed to redirect the immune system to destroy CD123-expressing leukemia cells. It is an antibody-like recombinant protein therapeutic that brings together leukemia cells and T-cells to eliminate cancerous cells. APVO436 is also intended to minimize the frequency and severity of CRS.

The primary objectives of the phase 1b trial are to determine the agent’s recommended phase 2 dose, the maximum tolerated dose according to the incidence of dose-limiting toxicities, and the safety profile. Secondary objectives include the maximum serum drug concentration, pharmacodynamics, immunogenicity, composite clinical remission among patients with a relapse, minimal residual disease status, and leukemia-free survival.

Patients needed to have histologically confirmed AML or MDS to be included in the study. Those with AML must have either refused or been ineligible for intensive chemotherapy or allogeneic transplant. Those with MDS must have more than 5% blasts in their bone marrow or any blasts in their peripheral blood and must have progressed on prior treatment with a hypomethylating agent.

Some of the other inclusion criteria are an ECOG performance status of 0 to 2, a life expectancy longer than 2 months in the opinion of the investigator, a white blood cell count no higher than 25,000 cells/mm³, and a creatinine clearance no more than 2 times higher than the upper limit of normal.

Exclusion criteria included any central nervous system disease, any history of seizures, and the presence of acute promyelocytic leukemia. Patients who had received prior anti-CD123 therapy, or who had any clinically significant graft-versus-host disease secondary to a prior allogeneic transplant, were also excluded. Receiving major surgery within 3 weeks of beginning study treatment or having any current autoimmune disorder requiring immunosuppressive therapy were also grounds for exclusion.

Reference

Aptevo announces positive duration of remission data from phase 1b expansion trial evaluating the bispecific APVO436 for AML. News Release. Aptevo Therapeutics Inc. July 18, 2023. Accessed July 19, 2023. https://bit.ly/3pMFokZ