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those ≥40 years-old, the oral/GI SRRT rate was 46% in the retrospective data versus 0% in subjects treated with AB-205 (unpublished; data in preparation).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 (20×10⁶ 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, DO³, Luke Mountjoy, DO⁴, Jordan Gauthier, MD^5,6, Bhagirathbhai Dholaria, MBBS⁷, Scott D. Rowley, MD, FACP⁸, Jeremy Pantin, MD, FACP⁹, Zachariah Defilipp, MD¹⁰, Monica Mead, MD¹¹, Mehrdad Abedi, MD¹², Rashmi Khanal, MD¹³, Umar Farooq, MD¹⁴, Joseph Bubalo, PharmD, BCPS, BCOP¹⁵, Carolyn Mulroney, MD¹⁶, Attaphol Pawarode, MD¹⁷, Muzaffar Qazilbash, MD, PhD¹⁸, Amer Beitinjaneh, MD¹⁹, Nancy Hardy, MD, FACP²⁰, Farhad Khimani, MD²¹, Tsiporah Shore, MD², Daniel O’Leary, MD²², Evandro Bezerra, MD²³, Jon Arnason, MD²⁴, Chukwuemeka Uzoka, MD²⁵, Jason Romancik, MD²⁶, and Paul Finnegan, MD²⁷

¹Memorial Sloan Kettering Cancer Center, New York, NY; ²Weill Cornell Medical College, New York, NY; ³City of Hope Comprehensive Cancer Center, Duarte, CA; ⁴Blood Cancer Institute, Denver, CO; ⁵Fred Hutchinson Cancer Research Center, Seattle, WA; ⁶University of Washington, Seattle, WA; ⁷Vanderbilt University Medical Center, Nashville, TN; ⁸Hackensack Meridian Health, Hackensack, NJ; ⁹TriStar Centennial Medical Center, Nashville, TN; ¹⁰Massachusetts General Hospital, Boston, MA; ¹¹UCLA Medical Center, Los Angeles, CA; ¹²UC Davis Comprehensive Cancer Center, Davis, CA; ¹³Fox Chase Cancer Center, Philadelphia, Pennsylvania; ¹⁴University of Iowa Hospitals & Clinics, Iowa City, Iowa; ¹⁵Oregon Health and Science University Hospital, Portland, OR; ¹⁶UC San Diego Health, San Diego, CA; ¹⁷University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; ¹⁸MD Anderson Cancer Center, Houston, TX; ¹⁹University of Miami Health System, Miami, FL;²⁰University of Maryland School of Medicine, Baltimore, MD; ²¹Moffitt Cancer Center, Tampa, FL;  ²²University of Minnesota, Minneapolis, MN; ²³Ohio State University, Columbus, OH; ²⁴Beth Israel Deaconess Medical Center, Boston, MA; ²⁵University of Illinois Cancer Center, Chicago, IL; ²⁶Emory University, Atlanta, GA; and ²⁷Angiocrine Bioscience, San Diego, CA

Go to Tandem Meetings – 2023