Aptevo Therapeutics’ investigational therapy APVO436 resulted in a patient’s complete disease remission in an ongoing trial in people with relapsed or refractory acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS), the company announced.
The announcement adds to an April update on the trial’s ongoing dose-escalation part, reporting early evidence of clinical response in an MDS patient on a lower dose of the therapy.
“We are greatly encouraged by the complete remission in the patient in cohort [group] 6, which is a wonderful outcome for them,” Marvin White, Aptevo’s president and CEO, said in a press release.
“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 [therapy],” he added. Of note, pharmacokinetics concerns a therapy’s movements in, through, and out of the body.
“We look forward to continuing the dose escalation and monitoring potential clinical responses as we advance through the upcoming dose cohorts,” White said.
Based on the company’s proprietary ADAPTIR technology platform, APVO436 is a lab-made bi-specific antibody designed to bind simultaneously to CD3 — a cell surface protein receptor in immune T-cells that activates their responses — and CD123, a protein highly present on the surface of blood cancer cells, including AML and MDS.
By binding to both proteins at the same time, APVO436 is expected to redirect T-cell attacks against CD123-positive cancer cells, killing them.
According to Aptevo, bi-specific antibodies based on their ADAPTIR technology may potentially be more convenient and cost-effective than other types of cancer immunotherapies, including CAR T-cell therapy.
Positive data from previous preclinical studies supported the launch of the open-label Phase 1/1b clinical trial (NCT03647800). It is evaluating APVO436’s safety, pharmacokinetics, pharmacodynamics (effects on the body), and clinical activity in up to 108 adults with relapsed or refractory AML or MDS. The study is still recruiting participants at sites across the U.S.
It is divided into two parts: a dose-escalation phase, meant to determine APVO436’s optimal dose; and an expansion phase, in which the recommended dose will be evaluated in two larger groups of patients.
During the first part, 10 groups of six people each are given increasing doses of APVO436. Once three people in a group complete their first treatment cycle and dose-limiting toxicities have been evaluated, treatment in the next dose group begins.
In the expansion phase, one group of 24 AML patients and another of 24 MDS patients will be treated with the recommended dose of APVO436, as established in the study’s first part.
APVO436 is administered directly into the bloodstream, every week, for six cycles of 28 days, until disease progression, intolerable toxicity, or withdrawal. Participants showing clinical benefit at the end of the sixth cycle may be given six additional therapy cycles.
According to the April trial update, dosing had been completed in five of the 10 dose-escalation phase groups. A dose-limiting toxicity was reported in one of the six patients in the fourth group, but no such toxicities were detected in any of group five participants. There were also no signs of neutralizing antibodies in the analyzed blood samples.
At that time, an MDS patient finishing an eighth treatment cycle showed a bone marrow complete response — defined as having less than 5% of myeloblasts in the bone marrow and at least a 50% reduction in their counts since treatment start. Myeloblasts are immature white blood cells found in abnormally high levels in AML and MDS patients.
The patient was still requiring platelet and red blood cell transfusions.
According to the latest update, treatment in group seven is ongoing, and a patient in group six achieved complete remission after two therapy cycles.
This patient’s bone marrow myeloblasts dropped from 29% at enrollment to 6% after the first cycle of APVO436, and to 0% after the second cycle. Platelet and neutrophil (a type of white blood cell) counts met complete remission criteria.
Researchers will continue to monitor patients’ responses through the tenth group in the dose-escalation phase, before moving to the expansion part of the trial.