Aptevo Therapeutics Announces Expansion Phase of Lead Anti-Leukemia Drug APVO436 in Adult Patients with Acute Myeloid Leukemia
Initiates Multi-Center, Multi-Arm Trial Using Active Dose Identified in the Dose Escalation Phase of the Trial
The dose expansion phase (Part 2), has been rationally designed to further evaluate the tolerability and clinical impact potential of APVO436 for indications of unmet and urgent medical need. During Part 2, the dose expansion phase of the study, a total of 90 AML patients will be enrolled into 5 cohorts of 18 patients each, as explained in the detailed and publicly available study information provided at CinicalTrials.gov (NCT03647800) The study will be conducted under an FDA-approved IND and has been Central IRB-approved. Patient enrollment is anticipated to commence in June. The goal of the expansion phase is to evaluate the safety and tolerability of APVO436 at the recommended Phase 2 dose level, when it is used as an adjunct to the standard of care and to obtain a preliminary assessment of the anti-leukemia activity of APVO436 containing experimental monotherapy and combination therapy modalities.
Protocol-specific training has started for the participating academic cancer centers in the US. Aptevo is planning to conduct Part 2 of the study at up to 20 clinical trial sites.
"The greatest challenge in AML is relapsed or refractory disease. For relapsed or refractory AML, there is no consensus on a single re-induction regimen" explained Dr.
Overview of Cohorts
In Cohort 1, AML patients in relapse will be treated with the standard chemotherapy drug cytarabine or the standard chemotherapy triple drug combination MEC (mitoxantrone, etoposide, cytarabine) plus APVO436. Also treated in this cohort will be patients with primary refractory AML whose leukemia failed to respond to frontline standard induction chemotherapy.
In Cohort 2, AML patients in first relapse will receive a combination of APVO436 + venetoclax + azacitidine. Also included in this cohort will be newly diagnosed AML patients with a poor prognosis who will receive this novel combination as their frontline induction regimen.
In Cohort 3, AML patients with poor prognosis who are newly diagnosed will receive their frontline chemotherapy to induce a remission and APVO436 will be added if there is evidence of residual leukemia remaining. Also included in this cohort will be AML patients who experienced an early first relapse within 1 year of receiving their frontline chemotherapy. Such patients are generally known to have a dismal outcome.
In Cohort 4, AML patients in 1st remission who have evidence of residual leukemia, also known as minimal residual disease (MRD), will receive the standard drug oral azacytidine in combination with APVO436.
In Cohort 5, AML patients in 2nd remission who are MRD+ will be treated with APVO436 monotherapy.
"New treatments are urgently needed for frontline adverse risk and relapsed AML populations and I look forward to working with
"This week has been exciting for Aptevo, as we announced both positive results from the dose escalation part of our Phase 1 trial and the initiation of the expansion phase. We are particularly excited about the fact that APVO436 did not cause severe neutropenia in any of the AML patients treated so far. This is a potentially paradigm-shifting discovery as it provides the unique opportunity to integrate APVO436 into standard treatment regimens that inherently cause severe neutropenia," said Mr.
Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo's lead proprietary drug candidate, APVO436 is a bispecific ADAPTIR that targets CD123 x CD3 and is designed to redirect the immune system of the patient to destroy leukemia cells expressing the target CD123 molecule on their surface. This antibody-like recombinant protein therapeutic is designed to engage both leukemia cells and T-cells of the immune system and bring them closely together to trigger a rapid and complete destruction of leukemia cells. APVO436 has been engineered using Aptevo's proprietary and enabling bioengineering methods and is designed to reduce the likelihood and severity of an unintended and potentially harmful activation of the immune system. APVO436 has been engineered to stay in the blood circulation long enough to locate, bind with and destroy target leukemia cells. APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.
Safe Harbor Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, Aptevo's expectations about the activity, efficacy and safety of its therapeutic candidates and potential use of any such candidates as therapeutics for treatment of disease, advancement of its clinical trials and its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "optimism," "potential," "designed," "engineered," "breakthrough," "innovative," "innovation," "promising," "plans," "forecasts," "estimates," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo's current intentions, beliefs and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement.
There are a number of important factors that could cause Aptevo's actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo's business or prospects; adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; adverse developments in the