On May 27, 2021 Aptevo Therapeutics Inc. ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIRTM and ADAPTIR-FLEXTM platform technologies reported that the company has initiated the expansion phase of lead anti-leukemia drug candidate, APVO436, in adult patients with acute myeloid leukemia (AML) with a multi-center, multi-arm trial using the active recommended dose identified in the dose escalation phase (Part 1) of the study (Press release, Aptevo Therapeutics, MAY 27, 2021, View Source [SID1234583271]). During Part 1, APVO436 exhibited a manageable side effect profile, encouraging single agent activity and a promising benefit to risk profile in relapsed AML patients. The Company has plans to submit data from the dose escalation phase for publication later this year.
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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. Fatih Uckun, leukemia expert and Chief Clinical Advisor. "By combining APVO436 with the standard of care, Aptevo hopes to develop an innovative approach that improves outcomes for patients with relapsed AML, who generally have a dismal prognosis," he stated.
Dr. Uckun explained further: "In addition, newly diagnosed AML patients with inherent drug resistance who have documented residual leukemia after standard frontline chemotherapy regimens, have a very poor prognosis and are in urgent need of therapeutic innovations. Part 2 of the Aptevo study will therefore seek proof of concept in the use of APVO436 as part of frontline multimodality regimens would enable the eradication of residual leukemia cells that have escaped standard chemotherapy. To this end we will carefully study the tolerability and clinical activity of APVO436 when used as rationally designed in each of the 5 cohorts of Part 2 of our Phase 1B study."
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 Dr. Uckun and other investigators for a step-wise evaluation of the clinical potential of APVO436", says Dr. Justin Watts, Associate Professor of Medicine at the University of Miami Sylvester Comprehensive Cancer Center.
"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. Marvin White, President and CEO of Aptevo. "The initiation of Part 2 in our APVO436 study emphasizes our commitment to advance our ADAPTIR and ADAPTIR-FLEX platforms as integral parts of a novel standard of care for the most difficult-to-treat forms of cancer. We look forward to sharing interim data from Part 2 of the trial, later this year."