Abstract:
Myeloablative conditioning or high-dose therapy followed by autologous hematopoietic cell transplantation (HDT-AHCT) is a standard of care (SOC) and potentially curative consolidation therapy for eligible patients diagnosed with aggressive lymphoma. Although effective in chemosensitive patients, HDT-AHCT is associated with severe regimen-related toxicities (SRRTs) that affect quality of life and may increase mortality risk (Olivieri et al., BBMT 2018). SRRTs occur due to the off-target cytotoxicity of HDT that involves damage to the microvasculature and the vascular stem cell niches of multiple organs. SRRTs predominantly affect organs with high cell turnover causing severe complications such as diffuse gastrointestinal (GI) mucositis (oral/GI SRRT) and delayed hematopoietic recovery. Rates and severity of toxicities increase with age, relevant to the demographics of the aging lymphoma population. Importantly, patients identify oral/GI SRRT as one of the most severe adverse effects experienced with HDT-AHCT (Stiff et al., BMT 2001). Notwithstanding, there are limited treatment strategies aimed at preventing SRRTs.
AB-205 is an experimental, engineered cell therapy that consists of allogeneic, human umbilical vein endothelial cells transduced with the pro-survival E4ORF1+ gene (E-CEL® cells). The proposed mechanism of action is paracrine in nature consisting of cell expression of reparative angiocrine factors which are thought to accelerate the repair injuries from off-target cytotoxicity of myeloablative conditioning. In a previously presented Phase 1/2 study [NCT03925935] in HCT-eligible patients with lymphoma, AB-205 was well tolerated and resulted in a 9% incidence of early oral/GI SRRT [defined as Grade ≥3 mucositis (M), nausea (N), vomiting (V) or diarrhea (D) in systemic lymphoma subjects conditioned with BEAM and BEAM-alternates (Phase 1/2 data is locked and analysis is in progress). This oral/GI SRRT incidence compared highly favorably to an incidence rate of 41% resulting from a contemporary, retrospective observational study conducted at two phase 1/2 sites (done concurrently during the conduct of the phase 1/2 study).
Here we report the study design of the AB-205 Phase III, randomized, double-blind, placebo controlled multi-center study (E-CELERATE) that has been initiated.
64th ASH Annual Meeting and Exposition – December 12, 2022
Michael Scordo, MD1,2, Geoffrey Shouse, PhD, DO3, Luke Mountjoy, DO4, Jordan Gauthier, MD5,6, Bhagirathbhai Dholaria, MBBS7,8, Scott D. Rowley, MD9, Jeremy M. Pantin, MD, FACP10, Zachariah Defilipp, MD11, Monica Mead, MD, BS12 and Paul Finnegan, MD13
1Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center/New York, New York, NY, 2Department of Medicine, Weill Cornell Medical College, New York, NY, 3Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 4Hematology Department, Colorado Blood Cancer Institute, Denver, CO, 5Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Seattle, WA, 6Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, 7Division of Hematology/Oncology, Department of Medicine, Vanderbilt School of Medicine, Nashville, TN, 8Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, 9Stem Cell Transplantation and Cellular Therapy Program, Hackensack University Medical Center, John Theurer Cancer Center, Hackensack, NJ, 10Department of Hematopoietic Cell Therapy, Sarah Cannon Center for Blood Cancer at TriStar Centennial Medical Center, Nashville, TN, 11Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, 12Department of Medicine, Division of Hematology/Oncology, UCLA Medical Center, Santa Monica, CA, 13Angiocrine Bioscience, San Diego, CA
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