Diane M. Simeone, MD, discusses the phase 1/2 EVEREST-1 trial evaluating the autologous CAR T-cell therapy A2B530 in patients with solid tumors.
Diane M. Simeone, MD, Laura and Isaac Perlmutter Professor of Surgery, Department of Surgery, professor, Department of Pathology, NYU Grossman School of Medicine, director, the Pancreatic Cancer Center, associate director, Translational Research, the Perlmutter Cancer Center, discusses the phase 1/2 EVEREST-1 trial (NCT05736731) evaluating the autologous CAR T-cell therapy A2B530 in patients with solid tumors.
The study is enrolling patients with solid tumors that express carcinoembryonic antigen (CEA) and have lost HLA-A*02 expression. To be eligible for enrollment, patients must have first undergone apheresis to store T cells for a future interventional study upon disease relapse during the BASECAMP-1 trial (NCT04981119). Through the apheresis and next-generation sequencing, the BASECAMP-1 trial is identifying patients who would be potential candidates to receive A2B530 in EVEREST-1, Simeone says.
BASECAMP-1 is enrolling a broad range of patients, and those that match the specific inclusion criteria of loss of HLA-A*02 expression and CEA overexpression will be eligible for EVEREST-1, Simeone notes. Although EVEREST-1 is currently limited to patients with a loss of HLA-A*02 expression, investigators plan to gradually broaden the HLA subtypes that will be eligible for the trial, Simeone adds, noting that the HLA-A*02 subtype accounts for approximately 30% of the United States population. The current inclusion criteria could create a funneling effect to include a smaller subset of patients; however, limiting enrollment to this subset of patients represents a good start for the study, Simeone expands.
As the approach broadens to include different activators or antigens expressed on the surface of tumor cells, this may increase the number of patients with solid tumors who will be eligible for enrollment, Simeone says. Investigators are also exploring approaches to best mitigate off-target effects of treatment with A2B530 so that the product can be delivered at a high payload while still allowing for the management of adverse effects associated with CAR T therapies, Simeone concludes.