Aptevo Therapeutics Inc., a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies, today announced the publication of a peer-reviewed research article in the prestigious oncology journal Cancers. The research article reports the results of a multi-institutional Phase 1 clinical study of Aptevo’s lead leukemia drug candidate APVO436 in 46 adult patients with relapsed or refractory AML or MDS.
“AML and MDS are common forms of blood cancer in adults. Patients with AML or MDS who relapse following available standard of care treatments have a dismal prognosis and they are in urgent need for new treatment options,” explained Dr. Fatih Uckun, a leukemia expert and Chief Clinical Advisor at Aptevo, who is the lead author of the new article. He added: “This study was undertaken to evaluate if AML or MDS patients who have failed the available standard treatment options could tolerate and potentially benefit from a new form of therapy which activates patient’s own immune system against AML cells. Specifically, APVO436 is a recombinant protein engineered to redirect host immune system to leukemic cells from patients with hematologic malignancies that express on their surface a protein known as the interleukin 3 receptor or CD123.”
A total of 46 relapsed AML/MDS patients received APVO436 as weekly intravenous (IV) infusions at 10 different dose levels. APVO436 exhibited a favorable safety profile with acceptable tolerability and generally manageable drug-related adverse events (AEs), and its maximum tolerated dose (MTD) was not reached at a weekly dose of 60 mcg. The most common APVO436-related AEs were infusion-related reactions (IRR) occurring in 13 (28.3%) patients and cytokine release syndrome (CRS) occurring in 10 (21.7%) patients. The incidence of severe CRS was 8.7%.
Promising clinical activity was observed in 11 of 40 patients (27.5%) evaluable for efficacy: Eight of 34 (23.5%) evaluable relapsed AML patients showed favorable responses including prolonged stable disease (SD), >50% reduction of leukemic cell count in the bone marrow with clearance of leukemic cells from the blood, partial remissions (PR), and complete remissions (CR). Seven of these 8 with favorable responses had failed 2-4 prior lines of anti-AML therapy and one 76 years old patient had relapsed after achieving a remission on frontline venetoclax plus decitabine therapy. Furthermore, 3 of 6 (50%) evaluable relapsed MDS patients had a marrow CR.
The median survival was >300 days for the 8 relapsed AML patients with a favorable response. By contrast, the median survival for the remaining 31 AML patients was 100 days. Five of the 8 AML patients with favorable responses remained alive at 110, 124, 323, 352, and 395 days, respectively.
A clinically active, so-called “recommended phase 2 dose (RP2D) level” was identified for further clinical development of APVO436. Of 9 patients treated at the RP2D level, 4 (44.4%) showed evidence of clinical activity: 2 AML patients achieved a CR, one MDS patient achieved a marrow CR, and the disease was stabilized in an AML patient with a time to progression of more than 7 months.
“The safety profile and preliminary evidence of efficacy of APVO436 in relapsed AML and MDS patients warrant further investigation of its clinical potential.” stated Dr. Uckun. “We are excited about the potential clinical impact of our lead leukemia drug candidate, and we are hopeful that the continued development of APVO436 may provide the foundation for a potentially more effective combination therapy as a new standard of care regimen that is less likely to fail.” added Marvin White, CEO of Aptevo.
