Allogene Starts Phase 2 Trial of Cema-cel CAR T for First-Line LBCL Treatment

Allogene Therapeutics Inc. and Foresight Diagnostics have announced the commencement of the pivotal Phase 2 ALPHA3 trial, which evaluates the use of cemacabtagene ansegedleucel (cema-cel) as part of the first-line treatment for newly diagnosed large B-cell lymphoma (LBCL) patients at risk of relapse following standard first-line treatment. This trial aims to incorporate Foresight's investigational CLARITY™ test to identify minimal residual disease (MRD) in patients, which signifies their likelihood of relapse.

Dr. David Chang, President, CEO, and Co-Founder of Allogene, emphasized the transformative potential of the ALPHA3 trial for first-line LBCL treatment. He highlighted that this investigational allogeneic CAR T product could streamline the complex logistics associated with autologous CAR T therapy, making it accessible within community settings. The trial focuses on offering this potentially curative treatment only to patients predicted to relapse.

The ALPHA3 trial will use the Foresight CLARITY™ MRD test, which has received Investigational Device Exemption (IDE) approval from the U.S. Food and Drug Administration. This test utilizes PhasED-Seq™ technology to detect MRD with high sensitivity. Upon detecting MRD after six cycles of R-CHOP or other standard chemoimmunotherapy regimens, cema-cel will be infused as a “7th cycle” of treatment. This consolidation treatment aims to improve first-line cure rates in LBCL patients.

Dr. Sandra Close, Chief Operating and Compliance Officer at Foresight Diagnostics, noted that the FDA's recent recommendation to include MRD as an endpoint in clinical trials for multiple myeloma underscores the importance of MRD detection in drug development. She believes that the Foresight CLARITY MRD platform could facilitate actionable treatment decisions by identifying residual disease levels that conventional methods may miss.

The ALPHA3 trial will be conducted across various cancer treatment centers, including community cancer centers where most first-line patients are treated. Approximately 240 patients will be enrolled in this randomized study designed to demonstrate a significant improvement in event-free survival (EFS) for those treated with cema-cel compared to the current standard of care, which involves observation. Interim efficacy analyses by an independent Data Safety Monitoring Board (DSMB) are scheduled for the first half of 2026, with the primary EFS analysis expected in the second half of 2026. A potential Biologics License Application (BLA) submission is anticipated in 2027.

Cema-cel, an investigational anti-CD19 AlloCAR T™ product, targets LBCL and received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA in June 2022 for third-line relapsed/refractory LBCL. The ongoing ALPHA3 trial, which started in June 2024, seeks to establish cema-cel as a standard part of first-line treatment for LBCL, administered immediately after detecting MRD following initial chemoimmunotherapy.

Allogene Therapeutics, based in South San Francisco, is a biotechnology company focused on developing allogeneic CAR T cell products for cancer and autoimmune diseases. Their goal is to provide readily available cell therapy on demand, increasing accessibility and reliability for more patients. Foresight Diagnostics, a privately-held cancer diagnostics company, specializes in liquid biopsy-based MRD detection, aiming to enable more personalized treatment approaches.

The ALPHA3 trial represents a significant step in improving first-line treatment outcomes for LBCL patients at risk of relapse, potentially setting a new standard in cancer care.