On November 23, 2021 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported a clinical update for the Company’s Phase 1b Expansion trial evaluating APVO436 in the treatment of acute myeloid leukemia (AML) (Press release, Aptevo Therapeutics, NOV 23, 2021, https://aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-therapeutics-reports-first-complete-remission-providing [SID1234595985]). Preliminary data observed to date includes one complete remission.
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A high-risk AML patient treated in Cohort 1 with a combination of chemotherapy plus APVO436 achieved a complete remission (CR) after one cycle of therapy. The chemotherapy regimen included the standard leukemia drugs Mitoxantrone, Etoposide, and Cytarabine. The patient tolerated treatment without evidence of overt toxicity.
The overarching goal of the Phase 1b expansion phase study is to determine if APVO436 treatments can improve the quality of remission in high-risk AML patients by reducing the residual chemotherapy-resistant measurable residual disease (MRD) burden. The quality of remission will be assessed using state-of-the art multiparameter flow cytometry methods for quantitative MRD assessment in a centralized laboratory.
MRD, previously known as minimal residual disease, in AML refers to leukemia cells that are present at very low numbers but can be detected using highly sensitive flow cytometric or genomic methods. A recent systematic review of the clinical significance of MRD in over 10,000 AML patients has demonstrated that achievement of MRD negativity is associated with superior leukemia-free survival and overall survival. Therefore, MRD status has emerged as an attractive and clinically meaningful end point that may allow for accelerated evaluation of novel therapies in AML (reference: Short et al., Association of Measurable Residual Disease with Survival Outcomes in Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. JAMA Oncol. 2020 Dec 1;6(12):1890-1899. Click here to view the publication: View Source
Aptevo believes that APVO436 has the potential to help AML patients achieve complete remissions without MRD and thereby reduce their risk of leukemic relapses. Aptevo also believes that the use of APVO436 for targeting MRD in AML may be associated with a very low risk of cytokine release syndrome (CRS) as well as an increased likelihood of responses as both CRS as well as responses are inversely correlated with the leukemia burden of the patients. If successful, deepening the remission to an MRD-negative remission using this strategy could translate into an improved overall survival in AML.
The Company recently published information about the compound’s favorable safety profile, characterized by a low incidence of CRS, and promising single agent activity of APVO436 in two back-to-back peer-reviewed publications in the prestigious oncology journal Cancers (Basel):
1. Uckun, F.M.; Lin, T.L.; Mims, A.; Patel, P.; Lee, C.; Shahidzadeh, A.; Shami, P.; Cull, E.; Cogle, C.R.; Watts, J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplasia. Cancers (Basel) 2021, 13, Aug 15;13(16):4113. Click here to view the publication: View Source
2. Uckun FM, Watts J, Mims AS, Patel P, Wang E, Shami PJ, Cull E, Lee C, Cogle CR, Lin TL. Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436. Cancers (Basel) 2021; 13(21):5287. Click here to view the publication: View Source
About APVO436
Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo’s lead proprietary drug candidate, APVO436 is a bispecific CD3xCD123 ADAPTIR that 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 the 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 CRS. APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.