Allogene Therapeutics (NASDAQ:ALLO) surged 36% on Monday after releasing positive interim data from its pivotal ALPHA3 study, showing that cemacabtagene ansegedleucel (cema-cel) delivered significantly higher minimal residual disease (MRD) clearance rates compared with observation.
The interim futility analysis revealed MRD clearance of 58.3% in the cema-cel arm versus 16.7% in the observation group, representing a 41.6% absolute improvement—well above the 25–30% threshold considered clinically meaningful in existing literature. The study focuses on patients undergoing first-line consolidation for large B-cell lymphoma.
At the first MRD assessment on Day 45, circulating tumor DNA (ctDNA) levels dropped by a median of 97.7% in patients treated with cema-cel, while the observation arm showed a median increase of 26.6%. The findings were based on 24 patients, evenly split between the two groups.
Safety data also appeared favorable, with no reported cases of cytokine release syndrome, neurotoxicity, graft-versus-host disease, or treatment-related serious adverse events. Notably, 10 of the 12 patients receiving cema-cel were managed entirely in outpatient settings following infusion.
Community cancer centers played a notable role in the study, accounting for around one-third of both patient screening and treatment administration, including sites with limited prior experience in CAR T therapies.
The ALPHA3 trial is currently underway at more than 60 sites and aims to enroll approximately 220 patients. Recruitment is expected to conclude by the end of 2027, with an interim analysis of event-free survival (EFS) planned for mid-2027 and the primary EFS readout targeted for mid-2028.
Event-free survival is the primary endpoint of the study, with progression-free survival and overall survival among the key secondary measures. The trial is designed to demonstrate a 50% reduction in the risk of EFS events, defined as the need for new anti-lymphoma therapy, disease progression, or death.