Dr Kirtane on the Design of the EVEREST-1 Trial Evaluating A2B530 in Solid Tumors

Kedar Kirtane, MD, assistant member, the Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, discusses the design of the phase 1/2 EVEREST-1 trial (NCT05736731), which is evaluating the autologous CAR T-cell therapy A2B530 in patients with advanced solid tumors.

EVEREST-1 features a unique design for a CAR T-cell therapy clinical trial, Kirtane begins. A master screening protocol serves as the first step for potential enrollment in the study, referred to as the BASECAMP-1 trial (NCT04981119). In the observational BASECAMP-1 study, patients with advanced solid tumors with a high risk of relapse are undergoing extensive screening to identify those with tumors expressing human leukocyte antigen (HLA) loss of heterozygosity.

During BASECAMP-1, enrolled patients are undergoing apheresis to store T cells for future use to produce A2B530 as part of EVEREST-1. Notably, there is no time limit between enrollment in BASECAMP-1 and EVEREST-1, and eligible patients will be allowed to enroll in EVEREST-1 upon disease progression. EVEREST-1 is including patients with colorectal cancer, pancreatic cancer, non–small cell lung cancer, and other solid tumors with CEA expression and a loss of HLA-A*02 expression.

A2B530 features a unique mechanism designed to distinguish tumor cells from healthy cells, Kirtane expands. The CAR T-cell therapy is meant to target tumors that express CEA and do not have HLA-A*02 expression. That mechanism inspired the observational BASECAMP-1 trial as a prescreening protocol to better identify patients who would be eligible to receive A2B530, allowing patients to enroll in EVEREST-1 following disease progression, Kirtane says.

Loss of heterozygosity is a common occurrence in patients with cancer, Kirtane continues, noting that it occurs in approximately 20% of patients with solid tumors. By identifying patients with this unique mutation, it allows EVEREST-1 to enroll patients more likely to benefit from this treatment, Kirtane concludes.