Allogene continues to investigate and characterize the chromosomal abnormality and its relationship to the gene editing.
The FDA has placed all of Allogene Therapeutics’ AlloCAR T trials on clinical hold after a chromosomal abnormality was observed in a patient dosed with ALLO-501A in the ALPHA2 trial (NCT04416984).1
The 11 CAR T programs placed on hold span tumor types, with phase 1 studies assessing the therapies in hematologic malignancies, solid tumors, and as a lymphodepletion agent. To date, over 100 patients have been dosed with AlloCAR T therapies.
“Patient safety is our highest priority, and we are committed to working closely with the FDA to evaluate any potential clinical implications of this finding, and determine next steps for advancing ALLO-501A and our clinical programs,” said Rafael Amado, MD, executive vice president, research and development, and chief medical officer, Allogene, in a statement.1
The patient, who had refractory stage 4 transformed follicular lymphoma and c-myc rearrangement, developed grade 1 cytokine release syndrome (CRS) and grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) following infusion of ALLO501A which was treated with high-dose steroid therapy. The patient then developed progressive pancytopenia and a bone marrow biopsy revealed the chromosomal abnormality with the presence of ALLO-501A CAR T cells as well as aplastic anemia. The patient did have a partial response to the therapy and subsequently underwent allogeneic stem cell transplantation.
“As a leading developer of allogeneic cell therapies, we recognize our added responsibility to fully assess all aspects of our therapies to advance the field. We are grateful for the partnership with the patient community, clinical investigators, our Scientific Advisory Board, and the FDA as we work diligently toward understanding the clinical significance of this finding and to support the development of allogeneic CAR T therapy for cancer,” Amado added.1
Allogene plans to consult with the FDA in the coming weeks. Meanwhile, the agency continues to review the ALPHA2 trial phase 1 materials submitted as it decides whether to clear a pivotal phase 2 trial for ALLO-501A. Allogene is investigating and characterizing the chromosomal abnormality, including its relationship to gene editing, clinical relevance, and clonal expansion.
Allogene had previously announced positive data on ALLO-501A at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting in June.2 These data demonstrated an overall response rate (ORR) of 75% and a complete response (CR) rate of 50% across histologies in CAR T naïve patients. The 6-month CR rate was 36% in CAR T naïve patients with LBCL. The longest ongoing CR was 15 months in both large B cell lymphoma (LBCL) and follicular lymphoma.
At the time of the announcement, no dose limiting toxicities, graft-vs-host disease, ICANS, or CRS were observed.
“We have made exceptional progress across our broad pipeline of AlloCAR T candidates, bringing our goal of revolutionizing cell therapy for patients with blood cancers and solid tumors closer to reality,” David Chang, MD, PhD, president, chief executive officer and co-founder, Allogene, had said in a statement at that time.2 “Our foundational and ongoing work has the potential to drive us toward an industry first - our planned pivotal trial for ALLO-501A in relapsed/refractory non-Hodgkin lymphoma which we expect to initiate at the end of this year.