Allogene Therapeutics Activates First Clinical Sites for Pivotal Phase 2 Trial of Cema-Cel

Allogene Therapeutics has activated three community cancer centres as the first clinical sites for a pivotal Phase 2 trial of cema-cel.

The trial, known as ALPHA3, will evaluate Cemacabtagene Ansegedleucel (cema-cel, formerly known as ALLO-501A) as a first line (1L) consolidation treatment for patients with large B-cell lymphoma (LBCL).

According to a press release published yesterday, the centres, which are now open for enrolment, include the Rocky Mountain Cancer Centers, Astera Cancer Care, and Norton Cancer Institute. Enrolment is expected to be complete in the first half of 2026, with potential submission of a biologics license application (BLA) in 2027.

The ALPHA3 trial aims to enrol newly diagnosed and treated LBCL patients who remain positive for minimal residual disease (MRD). When given as a “7^th cycle” of frontline treatment to eligible patients with MRD, consolidation treatment with cema-cel is anticipated to meaningfully improve 1L cure rates for LBCL patients who are likely to relapse.

ALLO-501A is a next-generation anti-CD19 AlloCAR T therapeutic candidate made from healthy donor cells. To develop ALLO-501A, donor cells are transduced with an integrating, self-inactivating recombinant lentivirus that harbours the anti-CD19 CAR.

To alleviate the risk of graft versus host disease that is associated with allogeneic cell therapies, the T cell receptor (TCR) gene, TRAC, in donor-derived cells is disrupted by TALEN editing. ALLO-501A is further edited by CD52 gene disruption, again using TALEN technology. CD52 disruption is a common feature in allogeneic CAR T therapies, in which an anti-CD52 monoclonal antibody (mAb) is administered to patients prior to treatment to suppress the patient’s immune system and allow the CAR T cells to engraft for long-term therapeutic effect. CD52 disruption renders ALLO-501A resistant to this treatment.

ALLO-501A builds upon Allogene’s earlier candidate ALLO-501, which is being assessed in the ongoing ALPHA trial. ALLO-501, which you can read about in one of our earlier posts, harbours rituximab recognition domains, while these are eliminated in ALLO-501A.

Rituximab is a CD20-specific monoclonal antibody that is widely used in the treatment of malignant lymphoma. In ALLO-501A, the rituximab recognition domains are eliminated, which Allogene Therapeutics believes will allow for use in a broader patient population, including Non-Hodgkin lymphoma patients who have recently been treated with rituximab.

In June 2022, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to cema-cel in third line (3L) r/r LBCL. The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL launched in June 2024. Allogene has oncology rights to cema-cel in the US, EU and UK with options for rights in China and Japan.

Read more in the official press release from Allogene Therapeutics here.