A Phase 3 Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of AB-205 Plus Standard of Care (SOC) Versus Placebo Plus SOC in Adults with Lymphoma Undergoing High-Dose Therapy and Autologous Hematopoietic Cell Transplantation (E-CELERATE; NCT05181540): Trial in Progress

Abstract: High-dose therapy and autologous hematopoietic cell transplantation (HDT-AHCT) is a standard of care (SOC) and potentially curative consolidation therapy for eligible patients with rel/ref lymphoma. While effective, HDT-AHCT is associated with severe regimen-related toxicities (SRRT) that affect quality of life and may increase mortality risk. SRRTs occur because of off-target cytotoxicity and vascular endothelial damage caused by HDT. Higher rates of SRRT occur in older patients because of age-related endothelial dysfunction, thus potentially limiting candidacy for AHCT. Moreover, there are limited treatment strategies to prevent SRRT. AB-205 is an engineered cell therapy consisting of allogeneic, human umbilical vein endothelial cells transduced with E4ORF1 (E-CEL ®  cells). AB-205’s mechanism of action is via induced expression of reparative angiocrine factors thought to accelerate tissue repair through the organ vascular stem cell niches. The proposed clinical indication of AB-205 is to prevent/reduce SRRT related to HDT. In a previously presented Phase 1/2 study [NCT03925935], AB-205 was well tolerated, resulting in a 9% incidence of oral/GI SRRT [defined as Grade ≥3 oral mucositis, nausea, vomiting and/or diarrhea] in 35 lymphoma subjects who received BEAM (or BEAM-like) conditioned-AHCT. The incidence of oral/GI SRRT in AB-205 subjects compared favorably to an incidence of 41% seen in a contemporary retrospective observational study conducted concurrently at 2 sites during the phase 1/2 study. The median time to neutrophil engraftment was accelerated by 2 days (10 vs. 12) and length of hospital stay was shortened by 3 days (12 vs.15), respectively. In those ≥40 years-old, the oral/GI SRRT rate was 46% in the retrospective data versus 0% in subjects treated with AB-205 ( unpublished; data in preparation ). Accordingly, a phase 3, randomized (1:1), double-blind, placebo-controlled study (E-CELERATE) was initiated to further investigate the efficacy and safety of AB-205 or placebo + SOC supportive prophylaxis in AHCT-eligible subjects with lymphoma (Figure 1). Key inclusion: age ≥40; diagnosis of lymphoma and a candidate for HDT-AHCT; ECOG ≤ 2; adequate organ function. Key exclusion: prior HCT; diagnosis of CNS lymphoma; other active malignancy; history of HIV. All subjects receive BEAM (or BeEAM) conditioning and SOC supportive prophylaxis. AB-205 IV (20×10 6  cells/kg) or placebo IV (diluent only) is administered on day 0 after stem cell infusion. The primary endpoint is complete response defined as the absence of oral/GI SRRT (defined above) from the time of HDT through day +21. Secondary endpoints include the duration of oral/GI SRRT; patient-reported symptom burden; duration of febrile neutropenia; time to engraftment. Approximately 140 adult patients will be enrolled across 30 sites in the U.S. Active recruitment and enrollment are on-going [NTC05181540]. Figure 1: AB-205-301 [NCT05181540] Study Schema 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. Tandem Meetings – Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR – February 16, 2023 Michael Scordo, MD 1,2 , Geoffrey Shouse, PhD, DO 3 , Luke Mountjoy, DO 4 , Jordan Gauthier, MD 5,6 , Bhagirathbhai Dholaria, MBBS 7 , Scott D. Rowley, MD, FACP 8 , Jeremy Pantin, MD, FACP 9 , Zachariah Defilipp, MD 10 , Monica Mead, MD 11 , Mehrdad Abedi, MD 12 , Rashmi Khanal, MD 13 , Umar Farooq, MD 14 , Joseph Bubalo, PharmD, BCPS, BCOP 15 , Carolyn Mulroney, MD 16 , Attaphol Pawarode, MD 17 , Muzaffar Qazilbash, MD, PhD 18 , Amer Beitinjaneh, MD 19 , Nancy Hardy, MD, FACP 20 , Farhad Khimani, MD 21 , Tsiporah Shore, MD 2 , Daniel O’Leary, MD 22 , Evandro Bezerra, MD 23 , Jon Arnason, MD 24 , Chukwuemeka Uzoka, MD 25 , Jason Romancik, MD 26 , and Paul Finnegan, MD 27 1 Memorial Sloan Kettering Cancer Center, New York, NY; 2 Weill Cornell Medical College, New York, NY; 3 City of Hope Comprehensive Cancer Center, Duarte, CA; 4 Blood Cancer Institute, Denver, CO; 5 Fred Hutchinson Cancer Research Center, Seattle, WA; 6 University of Washington, Seattle, WA; 7 Vanderbilt University Medical Center, Nashville, TN; 8 Hackensack Meridian Health, Hackensack, NJ; 9 TriStar Centennial Medical Center, Nashville, TN; 10 Massachusetts General Hospital, Boston, MA; 11 UCLA Medical Center, Los Angeles, CA; 12 UC Davis Comprehensive Cancer Center, Davis, CA; 13 Fox Chase Cancer Center, Philadelphia, Pennsylvania; 14 University of Iowa Hospitals & Clinics, Iowa City, Iowa; 15 Oregon Health and Science University Hospital, Portland, OR; 16 UC San Diego Health, San Diego, CA; 17 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; 18 MD Anderson Cancer Center, Houston, TX; 19 University of Miami Health System, Miami, FL; 20 University of Maryland School of Medicine, Baltimore, MD; 21 Moffitt Cancer Center, Tampa, FL;  22 University of Minnesota, Minneapolis, MN; 23 Ohio State University, Columbus, OH; 24 Beth Israel Deaconess Medical Center, Boston, MA; 25 University of Illinois Cancer Center, Chicago, IL; 26 Emory University, Atlanta, GA; and 27 Angiocrine Bioscience, San Diego, CA Go to Tandem Meetings – 2023

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