The phase 2 ALPHA2 trial of ALLO-501A should complete enrollment in 2024.
Patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) treated with the allogeneic chimeric antigen receptor (CAR) T-cell therapy ALLO-501/501A in the phase 1 ALPHA/ALPHA2 trials (NCT03939026, NCT04416984)had some durable responses with a manageable safety profile.
The updated data, as of April 20, 2023, are from 33 patients who have not previously received CAR T-cell therapy that were then treated with a single infusion or consolidation therapy (2 planned infusions) of ALLO-501/501A made with the Alloy™ manufacturing process material across different doses and lymphodepletion regimens. Both ALLO-501 and ALLO-501A are CD19-targeted CAR T-cell therapies, although the next-generation ALLO-501A eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, without concerns for recent rituximab exposure. ALLO-501A has been granted Regenerative Medicine Advanced Therapy designation by the FDA.
“We believe these data provide strong support for the ability of our product candidates to induce durable complete remissions at a rate similar to approved autologous CD19 CAR T therapies,” Zachary Roberts, MD, PhD, Executive Vice President, Research & Development and Chief Medical Officer, Allogene, said in a statement. “The design and execution of our Phase 1 ALPHA/ALPHA 2 trials enabled a systematic evaluation of potential Phase 2 treatment regimens. Based on these data, we were able to select an optimal dosing regimen that we believe will be capable of delivering the benefit of CAR T treatment to patients without the lengthy wait time and risk of manufacturing failure associated with autologous CAR T. We have now turned our attention to enrolling our potentially pivotal Phase 2 trials as quickly as possible.”
The participants received lymphodepletion with fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days; FCA90) and doses of ALLO-647 ranging from 13 mg/day to 30 mg/day for 3 days. The median time from enrollment to the start of therapy was 3 days, all patients successfully received therapy, and no patients received bridging therapy. Specifically, 12 patients were treated with a single dose of ALLO-501/501A and FCA90 lymphodepletion (phase 2 regimen), 6 patients weretreated with a single dose of ALLO-501/501A and FCA<90 lymphodepletion, and 15 patients were treated with consolidation dosing of ALLO-501/501A and split lymphodepletion.
Investigators found that 7 patients (58%) receiving the phase 2 regimen had a complete response (CR), 5 of which maintained the CR through month 6. Four of these patients have an ongoing CR and 1 had disease progression at 24 months. The median duration of response was 23.1 months with 3 patients in remission for over 24 months, with 1 response over 31 months. Across all patients, CR rate was 42% with 30% at 6 months. The results favored the FCA90 lymphodepletion regimen.
ALLO-501/ALLO-501A treatment was generally well tolerated with no incidences of grade 3 or greater cytokine release syndrome, no cases of immune effector cell-associated neurotoxicity syndrome, and no cases of graft versus host disease. Cytopenia and infections were manageable and similar to those seen with autologous CAR T cell therapies in this population.
The ALPHA/ALPHA2 phase 1 trials are evaluating the safety, tolerability, and preliminary efficacy at increasing dose levels of ALLO-501 and ALLO-501A and lymphodepletion regimens. The studies also evaluated various doses of ALLO-647, Allogene’s proprietary lymphodepleting antibody. The phase 2 ALPHA2 trial expects to complete enrollment in the first half of 2024, with trial sites in Europe, Canada and Australia to open during 2023.