How the ALPHA3 Trial May Transform the CAR T Landscape

Authored by David Chang , M.D., Ph.D., President and CEO

As we continue to pioneer the advancement of “off-the-shelf” allogeneic CAR T, I am excited to announce the initiation of our pivotal Phase 2 ALPHA3 trial. This groundbreaking trial will evaluate cemacabtagene ansegedleucel (cema-cel) – our innovative allogeneic CAR T product candidate – as part of the first line treatment regimen for patients with large B-cell lymphoma (LBCL) who are likely to relapse.

The potential impact of ALPHA3 is immense. Leveraging the Foresight CLARITY™ assay*, a new, ultra-sensitive test to identify patients with LBCL who have minimal residual disease (MRD), we aim to proactively offer this potentially curative modality to the approximately 30% of LBCL patients who are likely to relapse after they complete six cycles of R-CHOP or other standard 1L chemoimmunotherapy. The success of this trial could revolutionize the standard of care for LBCL patients, positioning cema-cel as part of the first line treatment plan with the potential to improve cure rates and leapfrog other CAR Ts currently offered in later line treatment.

The components needed to successfully launch ALPHA3 reflect decades of scientific advancement and build on the growing understanding that administering CAR T therapies to patients with low disease burden can improve safety and efficacy outcomes. But moving CAR T into earlier line treatment is not as easy as it sounds.

Currently, access to autologous CAR T therapies is limited primarily to large academic centers that manage later-line patients and have the resources and infrastructure to deliver treatment. However, 80% of patients with earlier stages of non-Hodgkin lymphoma (NHL), inclusive of LBCL, receive treatment closer to home in community cancer centers[1], where delivery of autologous therapies is far less feasible given their complexity and intense resource utilization.

ALPHA3 is designed with the specific attributes of cema-cel in mind. First and foremost, for the first time, the ALPHA3 study takes CAR T therapy to community cancer centers. As a one-time “off-the-shelf” treatment, administration of cema-cel does not require the complex logistics that have hindered CAR T adoption in community cancer centers where most earlier line patients seek care. And cema-cel’s Phase 1 safety profile, with low rates of CRS and ICANS, already permits its investigational use in the outpatient setting.

Consolidating response following an MRD+ result post 1L chemoimmunotherapy requires immediate and definitive action to prevent an impending relapse. Relapses tend to happen quickly – in many cases within just a few months[2]– making speed to treatment a critical success factor. Cema-cel treatment could begin within days following MRD test results. If ALPHA3 is successful, cema-cel could become the “7th cycle” of frontline treatment available to all eligible patients with MRD.

Our mission at Allogene Therapeutics has always been about pioneering new paths and democratizing access to CAR T therapy. With the initiation of the ALPHA3 trial, we take another significant step towards realizing this vision. As we embark on this exciting journey, I am filled with gratitude for the tireless efforts of our team, and that of Foresight Diagnostics as well as the trust placed in us by physicians and patients. Together, we are shaping the future of CAR T therapy.

Stay tuned for more updates on our progress at www.allogene.com!

*Foresight CLARITY™ is for Investigational Use Only

[1] Kite data on file.

[2] Allogene Corporate Presentation. May 2024.