KEY TAKEAWAYS
- The ALPHA2 phase I trial aimed to provide additional follow-up of participants in the first potentially pivotal trial for an allogeneic CAR T product.
- Pts with r/r LBCL received a 3-day LD regimen and a single dose of allogeneic CAR T cells produced by the Alloy manufacturing process.
- The study found that ALLO-501A was a safe and effective treatment for r/r LBCL.
Around 50% to 60% of relapsed/refractory large B-cell lymphoma (r/r LBCL) patients(pts) do not achieve complete response or relapse after standard treatments. Autologous anti-CD19 CAR T therapies have transformed care, but their patient-specific manufacturing and long wait times are limiting. Allogeneic off-the-shelf anti-CD19 CAR T treatment, like ALLO-501 and ALLO-501A, offers broader and faster access to one-dose curative treatment. Phase 1 data for these products show a manageable safety profile, no dose-limiting toxicities, and comparable efficacy to autologous CAR T therapy in r/r LBCL patients who haven’t received autologous CAR T before.
Researchers aimed to provide additional follow-up of participants in the first potentially pivotal trial for an allogeneic CAR T product.
Pts received a 3-day lymphodepletion regimen (FCA90), including fludarabine (F, 30 mg/m²/day), cyclophosphamide (C, 300 mg/m²/day), and ALLO-647 (A [anti-CD 52 mAb], 30 mg/day; total dose: 90 mg). Followed by a single dose of either ALLO-501 or ALLO-501A, both produced using Alloy manufacturing.
About 12 pts received the FCA90 lymphodepletion regimen and CAR T therapy, all receiving the product as specified within a median enrollment-to-lymphodepletion time of 3 days. The median follow-up time was 7.1 months (range: 1.4, 36.0), during which no Dose-Limiting Toxicities (DLTs), severe (Grade 3+) Cytokine-Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or Graft-Versus-Host Disease (GvHD) events occurred. An overall response rate (ORR) of 66.7% and a complete response rate (CR) of 58.3% were observed. The median Duration of Response (DOR) was 23.1 months. About 8 pts followed for 6 months, 62.5% had achieved CR, and 50.0% sustained CR through 6 months. Vector Copy Number Pharmacokinetics at Days 28 and 56 documented substantial and sustained expansion of CAR T cells were analyzed.
The study found ALLO-501A was a safe and effective treatment for r/r LBCL with a rapid treatment time and offered quick access to treatment within 3 days. These results endorse further assessment of ALLO-501A in the ongoing pivotal phase 2 trial (ALPHA2) for off-the-shelf allogeneic CAR T cells.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04416984
Frederick L. Locke, Lazaros J. Lekakis, Herbert Eradat, Javier Munoz, Michael Timothy Tees, Sven de Vos, Rajneesh Nath, Don A. Stevens, Shahbaz Malik, Leslie Popplewell, Mehdi Hamadani, Olalekan O. Oluwole, Miguel-Angel Perales, David Bernard Miklos, Paul Fisher, Lovely Goyal, Gregory Kaufman, Kazuharu Kai, Arun Balakumaran, and Sattva Swarup Neelapu. DOI: 10.1200/JCO.2023.41.16_suppl.2517 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 2517-2517.
