Allogene Therapeutics reports data from ALPHA3 trial

Allogene Therapeutics (ALLO) reported data from the planned interim futility analysis of its randomized Phase 2 ALPHA3 trial in first-line consolidation large B-cell lymphoma. At the protocol-defined data cutoff, which was triggered when the 24th patient completed Day 45 MRD assessment, 58.3% of patients in the cemacabtagene ansegedleucel arm achieved minimal residual disease negativity compared to 16.7% in the observation arm. This represents a 41.6% absolute difference in MRD clearance between the two arms. Based on literature, 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, 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. Cema-cel has been generally well-tolerated as of the data cutoff with no serious adverse events related to treatment. There were no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or graft-versus-host disease in the treatment emergent adverse events of special interest category, which captures adverse events associated with CAR T. Ten of 12 patients who received cema-cel were managed entirely outpatient post-infusion. The remaining two patients were briefly hospitalized for events deemed unrelated to cema-cel treatment. One patient in the observation arm was hospitalized for febrile neutropenia. This contrasts with the broader CAR T experience where hospitalization for toxicity management remains common, even in outpatient programs, with approximately 70%-90% of patients requiring admission and roughly 75% hospitalized for adverse events within 30 days. Both study arms consisted of patients with high-risk, aggressive lymphomas. Although limited by the small sample size, baseline characteristics show that a numerically greater number of patients in the cema-cel arm had more aggressive disease features, specifically stage III-IV disease and higher IPI scores, compared to the observation arm. A high-intensity variant of R-CHOP, DA-EPOCH-R, was the most commonly administered 1L therapy across both arms, with a slightly higher proportion of patients in the cema-cel arm receiving this first line treatment regimen. Twenty-five percent of patients in each arm entered the study after achieving a partial remission to 1L therapy. This interim futility analysis was based on the first 24 patients randomized and followed for post-treatment MRD assessment. MRD is assessed on Day 45, Month 3, and every 3 months during the first year of follow-up. The primary endpoint of EFS, along with key secondary endpoints of PFS and overall survival, remains blinded. The study is enrolling across more than 60 sites, with additional sites coming online, and is expected to enroll approximately 220 patients. Study accrual is anticipated to be complete by the end of 2027. The study is powered to detect a 50% reduction in the risk of EFS events. EFS events include the initiation of new anti-lymphoma therapy, disease progression, or death. The company anticipates an interim EFS analysis in mid-2027 and the primary EFS analysis in mid-2028. If positive, these results could support a biologics license application, or BLA, submission.