Acute Myeloid Leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production.
In patients unfit for intensive salvage chemotherapy, effective treatment options are lacking with typical complete response rates of just 20% and median overall survival of about 8 months only.
AB8939 is initially being developed in acute myeloid leukemia (AML) because cancer cells proliferate rapidly in this disease. AB8939 is 100 times more potent than doxorubicin (adriamycin), which is a reference drug in AML. Furthermore, AB8939 is not deactivated by myeloperoxidase enzyme, which is an advantage over vinca alkaloids (vincristine or vinblastine)123.
AB Science is evaluating AB8939 in a first-in-human clinical trial investigating its tolerability and efficacy in patients with acute myeloid leukemia in second- or third-line treatment and who are unfit to receive intensive chemotherapy. The strategy is to position AB8939 in patients with abnormal cytogenetics that make these patients unresponsive to first line therapy.
In recognition of the critical need for new treatments, AB8939 received orphan drug designation for AML from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Based on these promising preclinical results, AB Science initiated a Phase 1/2 study of AB8939 in relapsed or refractory acute myeloid leukemia.
The first part is a dose-escalation study designed to determine the safety and tolerability of AB8939 and to establish the recommended dose for the expansion study in the second phase.
The objective of the Phase 1 study is to determine the maximum tolerated dose (MTD) for the different treatment stages with AB8939.
The Phase 1 clinical trial of AB8939 has completed its first three stages. The first two stages were designed to determine the maximum tolerated dose (MTD) after 3 and 14 consecutive days of monotherapy. In both cases, the MTD was 21.3 mg/m².
The third stage, now completed, evaluated the combination of AB8939 and venetoclax. Six patients were treated at two dose levels (AB8939 for 14 days at a dose of 16 mg/m² + venetoclax for 14 days, followed by AB8939 for 14 days at a dose of 21.3 mg/m² + venetoclax for 14 days), with no dose-limiting or haematological toxicity observed, supporting the selection of the recommended dose for Phase 2. Four of the six patients achieved an objective response (one complete remission with incomplete haematological recovery and three partial responses), representing an overall response rate of 67%; the other two patients had stable disease, representing a disease control rate of 100%, after a single 14-day treatment cycle. The next stage (stage 4) will evaluate the triple combination of AB8939 + venetoclax + azacitidine.
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