First-Ever Complete Response in Lung Cancer Achieved with Novel Logic-Gated CAR-T Therapy A2B694

A2 Biotherapeutics today announced the safety and early efficacy data of its investigational CAR-T therapy A2B694 in the EVEREST-2 study. Analysis shows,A non-small cell lung cancer (NSCLC) patient treated with A2B694 achieved complete response (CR) on Day 90 post-infusion, which was confirmed by central assessment on Day 180.In the research of CAR-T therapy for solid tumors, complete remission cases are extremely rare.According to the press release, this is the first report of a lung cancer patient achieving CR after receiving CAR-T therapy.

A2B694 is an autologous logic-gated cell therapy under investigation, developed by A2 Biotherapeutics' proprietary Tmod platform.The Tmod platform achieves selective killing of tumor cells and protection of normal cells through a dual-receptor design, which includes an "activator" for recognizing tumor cells and a "blocker" for protecting normal cells.A2B694 consists of an activator targeting mesothelin (MSLN) and a targetHLA-A*02The blocker is composed of.In eligible patients, tumor cells are lostHLA-A*02, while normal cells retain this expression, thereby achieving therapeutic selectivity.

EVEREST-2 is a Phase 1/2 study designed to evaluate the safety and efficacy of A2B694. The study enrolls patients with colorectal cancer, pancreatic cancer, NSCLC, ovarian cancer, mesothelioma, and other solid tumors expressing MSLN while lacking HLA-A*02 expression. As of September 11, 2025, a total of 9 patients have been enrolled, including 3 cases of ovarian cancer, 2 cases of pancreatic cancer, and one case each of NSCLC, colorectal cancer, gastroesophageal cancer, and mesothelioma. Dosing includes three levels: 1x10⁸ (n=3), 2x10⁸ (n=4), and 4x10⁸ (n=2). One patient each in the 1x10⁸ and 2x10⁸ dose groups received a half-dose due to body weight as per the trial protocol. The maximum tolerated dose (MTD) has not yet been reached, and the study plans to further evaluate doses up to 14x10⁸ during the dose escalation phase.

Image Source: 123RF

This publication presents a case of a patient with advanced metastatic NSCLC carrying co-mutations (KRAS G12V/STK11), a subtype typically resistant to chemo-immunotherapy combination treatments and associated with poor prognosis. After showing no response to the standard first-line regimen (carboplatin + pemetrexed + pembrolizumab), the patient was enrolled in the EVEREST-2 trial.

On Day 90 after infusion of A2B694, the patient achieved complete response based on RECIST 1.1 criteria and was confirmed by central review on Day 180.Day 190 PET-CT scan showed no evidence of disease.Tumor gene mutations initially detected through circulating tumor DNA (ctDNA) at the time of diagnosis were no longer detected at the 6th and 8th months post-treatment.On day 243, the patient experienced an isolated central nervous system (CNS) relapse while extracranial disease remained in complete remission (CR, based on the Response Assessment in Neuro-Oncology Brain Metastases [RANO-BM] criteria). The patient subsequently received dexamethasone and Gamma Knife radiosurgery. A PET-CT scan on day 284 continued to show no evidence of disease. By the 12th month, CT imaging revealed no new lesions.

The trial results showed that A2B694 had controllable safety and good tolerability. The lymphodepletion procedure performed prior to A2B694 administration was also well-tolerated, characterized by typical transient cytopenia. No dose-limiting toxicity (DLT) or cytokine release syndrome (CRS) cases were observed in the study.

References:

[1] A2 Biotherapeutics Presents Initial Safety and Efficacy Data from Ongoing Phase 1/2 EVEREST-2 Study, Including First Report of a Complete Response to CAR T-Cell Therapy in a Patient with NSCLC. Retrieved November 7, 2025 from https://www.businesswire.com/news/home/20251031980313/en/A2-Biotherapeutics-Presents-Initial-Safety-and-Efficacy-Data-from-Ongoing-Phase-12-EVEREST-2-Study-Including-First-Report-of-a-Complete-Response-to-CAR-T-Cell-Therapy-in-a-Patient-with-NSCLC