ALLO-647

P2, N=250, Recruiting, Allogene Therapeutics

P1/2, N=6, Terminated, Allogene Therapeutics | N=136 --> 6 | Trial completion date: Jul 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Oct 2023; Terminated (Halted Prematurely)

P2, N=70, Active, not recruiting, Allogene Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2025 --> Feb 2024

P1, N=120, Recruiting, Allogene Therapeutics | Trial primary completion date: Dec 2022 --> Aug 2025

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-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.

Approval of two CD19-targeting autologous CAR Ts, Kymriah® and Yescarta®, has been followed with promising results from BCMA autologous CAR T clinical trials, showing that activity can extend to other targets...Cellectis’ TALEN® gene-editing was used to inactivate the TRAC and CD52 loci with the intent to minimize the risk of graft-versus-host disease and to confer resistance to ALLO-647, an anti-CD52 antibody that can be used as part of the conditioning regimen to deplete host alloreactive immune cells potentially leading to increased persistence and efficacy of the infused allogeneic cells...No detectable CD70 was observed by flow cytometry on purified CD34+ cells from 14 healthy donors. Taken together, our results support clinical development of CD70 AlloCAR T therapy for the treatment of AML.

These include: FCA (fludarabine (F) 90 mg/m2, cyclophosphamide (C) 900 mg/m2, and ALLO-647 (A) 39 mg divided over 3 days), FCA+ (same F and C but ALLO-647 (A+) dose of 90 mg divided over 3 days); as well as CA (same C and A divided over 3 days, but no F given)...Three episodes were Grade 1 and 1 was Grade 2 (Lee Grading); all resolved without tocilizumab or corticosteroids...Updated safety, efficacy, PK/PD data will be presented. Clinical trial information: NCT04093596.