APVO436, an investigational therapy for acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS), is showing safety and evidence of clinical activity in these patients, according to preliminary data from a Phase 1/1b trial, its developer, Aptevo Therapeutics, announced in a release.
APVO436 is a man-made, bi-specific antibody designed to bind simultaneously to CD123, a protein found in high levels on cancer cells, and CD3, a protein receptor found on the surface of immune T-cells. By binding to both proteins at the same time, APVO436 aims to activate and instruct T-cells to attack and destroy cancer cells.
The safety, clinical activity, and pharmacological properties of APVO436 are being investigated in this open-label trial (NCT03647800) in several groups of AML and MDS patients. The study, which may still be recruiting participants at sites in the U.S., is expected to enroll about 108 patients.
The study is divided into two parts. During the first dose-escalation phase, 10 groups of patients, with six people per group, are being given 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.
The dose-escalation phase will be followed by an expansion phase, in which two groups of 24 AML and 24 MDS patients will be treated with the recommended dose of APVO436, as established in the study’s first part. Treatment will be administered intravenously, every week, for six cycles of 28 days, 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.
So far, 19 patients were enrolled and treated with APVO436 in the study. Dosing has been completed in five groups of patients participating in dose-escalation phase, with a sixth group scheduled to start treatment.
Dose-limiting toxicities were not reported in any of the patients from group 5, the latest dose group. However, one of the six patients from the fourth group experienced a dose-limiting toxicity. No signs of neutralizing antibodies were found in any of the 17 patient blood samples gathered and analyzed in the study to date.
An MDS patient is currently finishing an eighth treatment cycle. A preliminary analysis shows that, despite requiring platelet and red blood cell transfusions, this patient attained a marrow complete response. In order to attain this response, a person must have less than 5% of myeloblasts (immature white blood cells) in their bone marrow, and have at least a 50% reduction in their levels since the beginning of treatment.
“The evolving data from our Phase 1 study of APVO436 continues to look promising. While still preliminary, we are encouraged by the early evidence of a clinical response observed with APVO436 for a patient in cohort 4,” Marvin L. White, president and CEO of Aptevo Therapeutics, said in a press release.
“Notably, we believe this is a sub-therapeutic dose, so the potential clinical activity observed is especially intriguing,” he added. “Importantly, we are now in a critical phase of the study, as pharmacokinetic modelling suggests that dosing in cohorts 5 through 8 is in a therapeutic range, which could result in potential clinical activity of the drug.”
APVO436 is based on the company’s proprietary ADAPTIR technology platform for developing immunotherapy candidates. According to Aptevo, bi-specific antibodies based on their ADAPTIR technology may potentially be more convenient and cost-effective compared to other types of cancer immunotherapies, including CAR T-cell therapy.