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Clinical Response after Allogeneic CAR T Cell Therapy Is Linked to Expansion of Identical CD8+ Effector-like T Cell Clones (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3684; P1/2 We identified patients with relapsed/refractory large B-cell lymphoma treated on the ALPHA-2 phase 1 trial (NCT04416984) with a single lot of ALLO-501A, a healthy donor-derived CD19 CAR T with T cell receptor (TCR) and CD52 knockout using Cellectis technologies...Moreover, our data highlight clones with effector-like molecular states as a key subset which could mediate antitumor responses to allogeneic CAR T cell products. These findings, as well as the presence of this phenotype in donor PBMCs prior to manufacturing, carry important implications for future development of these therapies.
- |||||||||| ALLO-647 / Allogene Overland Biopharm, cemacabtagene ansegedleucel (ALLO-501A) / Allogene Therap
Enrollment closed, Trial primary completion date, CAR T-Cell Therapy: EXPAND: Evaluation of Lymphodepletion With ALLO-647 in Adults With R/R Large B Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy (clinicaltrials.gov) - May 30, 2024 P2, N=70, Active, not recruiting, These findings, as well as the presence of this phenotype in donor PBMCs prior to manufacturing, carry important implications for future development of these therapies. Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2025 --> Feb 2024
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Cellular Mechanisms Affecting Allogeneic CAR T Cell Expansion and Rejection in Large B-Cell Lymphoma (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6288; P1/2 We identified 11 patients with relapsed/refractory large B-cell lymphoma treated on the ALPHA-2 phase 1 trial (NCT04416984) with ALLO-501A, a healthy donor-derived CD19 CAR T with T cell receptor (TCR) knockout...We revealed the impact of recipient alloreactive CD8 + T cells in allogeneic CAR T rejection and identified expansion of identical allogeneic CAR T clonotypes with retained clonal hierarchy in multiple patients. While patient factors such as tumor burden and target antigen expression likely play a role as well, our results suggest that strategies to eliminate alloreactive recipient cells and enhance allogeneic CAR T fitness through improved product design, manufacturing and lymphodepletion could improve allogeneic CAR T expansion, persistence and efficacy.
- |||||||||| ALLO-647 / Allogene Therap, ALLO-501 / Allogene Therap
ALLO-647 for Lymphodepletion in the Allogeneic CAR T Setting: Safety Experience with ALLO-501/501A in Patients (Pts) with Relapsed/Refractory (r/r) Large B-Cell and Follicular Lymphomas (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2530; P1, P1/2 While patient factors such as tumor burden and target antigen expression likely play a role as well, our results suggest that strategies to eliminate alloreactive recipient cells and enhance allogeneic CAR T fitness through improved product design, manufacturing and lymphodepletion could improve allogeneic CAR T expansion, persistence and efficacy. Updated phase 1 data for ALLO-501 (ALPHA; NCT03939026) and ALLO-501A (ALPHA2; NCT04416984) showed that administration of anti-CD19 allogeneic CAR T product following use of lymphodepletion that includes ALLO-647 plus fludarabine and cyclophosphamide provided durable responses and an acceptable safety profile in CAR T-cell
- |||||||||| ALLO-501 / Allogene Therap
DURABLES RESPONSES ACHIEVED WITH ANTI-CD19 ALLOGENEIC CAR T ALLO-501/501A IN PHASE 1 TRIALS OF AUTOLOGOUS CAR T-NA (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1418; P1, P1/2 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. A single dose of AlloCAR T therapy following FCA90 conditioning provided durable responses with a manageablesafety profile in autologous CAR T-na
- |||||||||| ALLO-647 / Allogene Overland Biopharm, cemacabtagene ansegedleucel (ALLO-501A) / Allogene Therap
Enrollment open, CAR T-Cell Therapy: EXPAND: Evaluation of Lymphodepletion With ALLO-647 in Adults With R/R Large B Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy (clinicaltrials.gov) - Apr 13, 2023 P2, N=70, Recruiting, In these two multicenter, single-arm, open-label, phase 1 trials, a cohort of autologous CAR T-na Not yet recruiting --> Recruiting
- |||||||||| ALLO-647 / Allogene Overland Biopharm, cemacabtagene ansegedleucel (ALLO-501A) / Allogene Therap
Enrollment closed, CAR T-Cell Therapy: ALPHA-2: Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2) (clinicaltrials.gov) - Oct 14, 2021 P1/2, N=30, Active, not recruiting, Currently, an ALLO-501A Phase 2 trial is planned. Recruiting --> Active, not recruiting
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