P1125: Durables Responses Achieved With Anti-cd19 Allogeneic Car T Allo-501/501a in Phase 1 Trials of Autologous Car T-naïve Patients With Relapsed/refractory Large B-cell Lymphoma (r/r Lbcl)
Year: 2023
Type: article
Study design: Clinical Trial
Abstract: Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Despite recent progress in treating LBCL, approximately 50% to 60% of pts will either not achieve a complete response (CR) or will relapse with current first- or second-line treatments and require additional therapy. With their unmatched efficacy, autologous anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized the care of patients whose disease progresses following standard therapies; however, patient-specific manufacturing processes and long wait times to treatment initiation prevent broader and more equitable use of these agents. In contrast, allogeneic (healthy-donor-derived), off-the-shelf CAR T cells promise to provide more patients with rapid access to one-dose treatment with curative intent. ALLO-501/501A is a pre-manufactured, allogeneic, CD52-knock-out/TCRα-knock-out, anti-CD19 CAR T cell product that uses Cellectis’ technologies. Conditioning with a regimen of fludarabine (F)/cyclophosphamide (C)/ALLO-647 (A, a humanized anti-CD52 monoclonal IgG1) targets host CD52+ immune cells for elimination while allowing subsequently infused CD52-knock-out ALLO-501/501A cells to persist. TCR-knock-out prevents the host immune system from recognizing MHC disparities between donor and host cells, and greatly reduces the risk of graft-versus-host disease (GvHD). Initial phase 1 data for the anti-CD19 AlloCAR T™ products ALLO-501 (NCT03939026) and successor ALLO-501A (NCT04416984) demonstrated a manageable safety profile with no dose-limiting toxicities (DLTs); efficacy outcomes were comparable to published results for autologous CAR T therapy in pts with r/r LBCL. Aims: This update provides data on the durability of response with the optimized AlloCAR T regimen (ALLO-501/501A following conditioning with ALLO-647 in FCA) that will be evaluated further in phase 2 trials. Methods: In these two multicenter, single-arm, open-label phase 1 trials, autologous CAR T-naïve pts with r/r LBCL underwent 3-day lymphodepletion (LD) followed by a single dose of ALLO-501/501A to identify the optimal regimen. FCA90 conditioning (F 30 mg/m2/day; C 300 mg/m2/day; A 30 mg/day [total dose: 90 mg]) followed by a single dose (120 X 106 CAR+ cells) of ALLO-501 or ALLO-501A produced by the Alloy manufacturing process was selected as the optimal regimen for development. Results: As of the Jan 26, 2023, cutoff, 12 pts received the FCA90 LD regimen and AlloCAR T therapy; 100% received the product per specifications with a median time of 3 days from enrollment to LD. Median follow-up time was 7.1 months (range: 1.4, 36.0). No DLTs were observed nor were any events of severe (Gr3+) cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS); no GvHD events occurred. In this cohort of 12 pts, the overall response rate was 66.7% with 58.3% achieving a best overall response of CR. Among pts with the opportunity to be followed for 6 months, 5 of 8 (62.5%) achieved CR and 4 of 8 (50.0%) maintained CR through 6 months with the longest CR ongoing at 36 months; median duration of response (DOR) was 23.1 months. Summary/Conclusion: A single dose of AlloCAR T therapy following FCA90 conditioning provided durable responses with a manageable safety profile in autologous CAR T-naïve pts with r/r LBCL. Among 8 pts who received FCA90 and ALLO-501/501A and had the opportunity to be evaluated for 6 months, 50% maintained that response for at least 6 months, with a median DOR of 23.1 months. These findings support broader evaluation of ALLO-501A/ALLO-647 in the ongoing, first potentially pivotal phase 2 trial (ALPHA2) of AlloCAR T therapy. Keywords: CAR-T, Allogeneic, Clinical trial, Diffuse large B cell lymphoma
Source: HemaSphere
Authors: Javier Munoz, Frederick Locke, Lazaros Lekakis, Herbert Eradat, Michael Tees, Sven de Vos, Rajneesh Nath, Don Stevens, Shahbaz Malik, Leslie Popplewell, Mehdi Hamadani, Olalekan Oluwole, Miguel-Angel Perales, David Miklos, Paul Fisher, Lovely Goyal, Lynn Navale, Gregory Kaufman, Kazuharu Kai, Arun Balakumaran, Sattva Neelapu
Institutions: Mayo Clinic Comprehensive Cancer Center (Arizona), Moffitt Cancer Center, University of Miami, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, Colorado Blood Cancer Institute, Banner Health, Norton Healthcare, St David's Medical Center, City Of Hope National Medical Center, Medical College of Wisconsin, Vanderbilt University Medical Center, Memorial Sloan Kettering Cancer Center, Stanford University, Allogene Therapeutics (United States), The University of Texas MD Anderson Cancer Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4385667240