Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, today reported data from the planned interim futility analysis of its pivotal, randomized Phase 2 ALPHA3 trial in first-line (1L) consolidation large B-cell lymphoma (LBCL).

At the protocol-defined data cutoff, which was triggered when the 24th patient completed Day 45 MRD assessment, 58.3% (7/12) of patients in the cemacabtagene ansegedleucel (cema-cel) arm achieved minimal residual disease (MRD) negativity compared to 16.7% (2/12) in the observation arm. This represents a 41.6% absolute difference in MRD clearance between the two arms. Based on literature,1 2 3 a difference in percentage points of 25-30% in the MRD clearance could translate into meaningful clinical benefit at study completion. In addition, at the first MRD assessment (Day 45), plasma ctDNA levels decreased from baseline by a median of 97.7% in the cema-cel arm compared to a 26.6% median increase in the observation arm. The Company believes these interim data provide initial support for cema-cel's potential as a novel strategy for treating high-risk patients at the end of first-line treatment.

MRD status post-treatment has emerged as a strong predictor of relapse in LBCL, creating a potential opportunity to intervene earlier in the course of disease, when disease burden is low, but the risk of progression remains high.4 5 The ALPHA3 trial is the first randomized study in LBCL designed to assess whether MRD-guided intervention before relapse can eliminate residual disease and potentially prevent recurrence. The study identifies high-risk patients using Natera's CLARITY™ MRD assay which is powered by its phased variant MRD technology. Patients with LBCL who have completed curative-intent treatment in both front-line and later line settings, including autologous CAR T therapy, and who achieve MRD negative status by technology have demonstrated improved progression-free survival (PFS) and EFS compared to those who do not attain MRD-negative status.