ALLO-501A received RMAT designation from the FDA in June 2022.
Allogene Therapeutics has initiated a phase 2 clinical trial (ALPHA2) for ALLO-501A, an investigational allogeneic anti-CD19 chimeric antigen T-cell (CAR-T) therapy, which will treat patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL).1
ALLO-501A was previously evaluated in a phase 1 clinical trial (NCT04416984) along with ALLO-647, an investigational anti-CD52 monoclonal antibody added to the fludarabine/cyclophosphamide lymphodepletion regimen with theintention of improving expansion, persistence, and clinical outcomes for the CAR-T therapy. Data from the phase 1 trial, which were presented at an oral session of the American Society of Hematology (ASH) annual meeting in December 2021, demonstrated that among the LBCL CAR-T naïve participants treated, no relapses occurred in patients who were in a complete response (CR) 6 months after dosing.2 Patients had continuing CRs for up to over 15 months. In terms of safety, the patients did not experience any dose limiting toxicities or graft versus host disease, and it was reported that grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and grade 3 cytokine release syndrome (CRS) were minimal. Additionally, it was noted that almost all of the enrolled patients received therapy with the median time from enrollment to treatment beginning being 2 days.
“We are proud to initiate the industry’s first potentially pivotal phase 2 trial for an allogeneic CAR-T product,” David Chang, MD, PhD, president, chief executive officer, and co-founder, Allogene Therapeutics, said in a statement.1 “This milestone paves the road for both ALLO-501A and our broader pipeline of innovative products with the potential to greatly increase patient access to cell therapy. It is a culmination of years of hard work and perseverance, which could only be accomplished in collaboration with our dedicated staff, investigators, clinical trial site coordinators, regulatory authorities, and most importantly the patients who have participated in our studies.”
The new phase 2 study will treat approximately 100 patients with a single dose of 120 million CAR+ cells. The lymphodepletion regimen (FCA90) is planned to consist of fludarabine (30 mg/m2/day x 3 days), cyclophosphamide (300 mg/m2/day x 3 days), with 90mg of ALLO-647. Participants will be required to have received 2 or more previous lines of therapy. Patients who have previously been treated with anti-CD19 therapy will be excluded from the study. Objective response rate (ORR) will serve as the trial’s primary end point.
Allogene Therapeutics is also launching a separate clinical trial, EXPAND, for ALLO-647. It is focused on evaluating ALLO-647's safety and contribution to the standard lymphodepletion regimen and will seek to recruit approximately 70 patients with r/r LBCL. Participants will be divided into an experimental arm, which will treat patients with the same lymphodepletion regimen as the ALPHA2 trial (including ALLO-647), and a control arm which will utilize a lymphodepletion regimen with fludarabine and cyclophosphamide alone. After the lymphodepletion regimen, participants will be treated with the same dose of ALLO-501A as in the ALPHA2 trial.
In October of last year, the FDA placed all of Allogene Therapeutics’ AlloCAR T trials on hold following a case of chromosomal abnormality observed in a patient who received ALLO-501A in the phase 1 clinical trial.3 However, the hold was lifted in January 2022 after it was concluded that the chromosomal abnormality was not related to Allogene Therapeutics’ manufacturing process and that it did not have clinical significance.4 ALLO-501A later received regenerative medicine advanced therapy (RMAT) designation for r/r LBCL from the FDA in June 2022.2
“Patients who are eligible for autologous CAR-T therapy are often faced with treatment delays and manufacturing failures, placing them at risk for disease progression and disease-related complications,” Rafael Amado, MD, executive vice president of Research and Development and chief medical officer, Allogene Therapeutics, said in a June 2022 statement.2 “We look forward to initiating our pivotal trial on ALLO-501A and making this innovative product candidate readily available to patients.”