Allogene Therapeutics, Inc. announced its 2024 Platform Vision that redefines the future of CAR T by leveraging the unique attributes of allogeneic CAR T products. The Foundation: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL): In a commanding pivot for the CD19 program, the Company will focus development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) as part of the first line (1L) treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy. The design of the ALPHA3 1L consolidation trial builds upon the results demonstrated in the Phase 1 ALPHA2 trial and leverages an investigational cutting-edge diagnostic test developed by Foresight Diagnostics to identify patients who have minimal residual disease (MRD) at the completion of 1L chemoimmunotherapy for treatment with cema-cel.

Although 1L R-CHOP is curative for many with LBCL, approximately 30% of patients who initially respond will relapsei. The standard of care after 1L treatment has been simply to ?watch and wait? for the disease to relapse.

ALPHA3 takes advantage of cema-cel as a one-time, off-the-shelf treatment that can be administered immediately upon discovery of MRD following six cycles of R-CHOP, positioning it to become the standard ?7th cycle? of frontline treatment available to all eligible patients with MRD. ALPHA3 builds on the growing understanding that administration of CAR T therapies to patients with low disease burden improves both safety and efficacy outcomes.

Cema-cel?s Phase 1 safety profile, with low rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), already permits its use in the outpatient setting in relapsed/refractory (r/r) patients and may further improve in patients with no radiological evidence of disease. Start-up activities for the ALPHA3 trial have been initiated. The study will randomize approximately 230 patients who are MRD positive at the end of 1L therapy to either consolidation with cema-cel or the current standard of care (observation).

The design, with a primary endpoint of event free survival (EFS), will initially include two lymphodepletion arms (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647). The outcome of this pivotal trial could allow cema-cel to be embedded in the 1L setting to boost cure rates, potentially rendering later-line treatment obsolete, and making cema-cel available in community cancer centers where most earlier line patients seek care. As a result of this differentiated vision for cema-cel which competitively places its use ahead of other CAR T therapies, the Company will focus on quickly advancing this market-defining ALPHA3 trial and deprioritize the currently enrolling third line (3L) ALPHA2 and EXPAND trials.

The Higher Bar: ALPHA2 Cema-Cel Trial in Chronic Lymphocytic Leukemia (CLL): There is a growing need for effective treatment in CLL post-Bruton tyrosine kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitor (BCL2i) therapies. While recent autologous CD19 CAR T data has been a positive step for patients with r/r CLL, these therapies are still not meeting the efficacy bar or expectations set in r/r LBCL. This is likely due in part to T cell dysfunction and high circulating tumor burden in CLL, making the isolation of functional T cells for autologous CAR T manufacturing difficult.

There is strong scientific rationale to believe that an AlloCAR T? product derived from healthy donor cells could raise the bar and potentially create a clinically meaningful advance for these late-stage patients, with a one-time dose and simpler administration and logistics. The new Phase 1 ALPHA2 cohort of 12 patients treated with the investigational product cema-cel provides the opportunity to set a higher bar where patients with CLL are not reliant on their own T cells? fitness to benefit from the curative potential of CAR T. This study, driven by investigator enthusiasm, will leverage currently active ALPHA2 trial sites in the U.S. which should allow it to advance quickly.

It is expected to begin enrolling in first quarter 2024 with initial data projected by YE 2024.