NATIONAL HARBOR, Md. — A2 Biotherapeutics, Inc. (A2 Bio) reported new safety and early efficacy data from the ongoing Phase 1/2 EVEREST-2 study (NCT06051695) evaluating its lead logic-gated CAR T-cell therapy, A2B694, for solid tumors. The results were presented at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), where the abstract was selected among the Top 150 submissions.
The study includes what is believed to be the first reported complete response to a CAR T-cell therapy in a patient with non-small cell lung cancer (NSCLC). The patient had progressive metastatic disease with KRAS G12V and STK11 co-mutations, an aggressive subtype that is typically resistant to treatment and associated with poor outcomes. The patient was refractory to first-line therapy prior to receiving A2B694. Following a single infusion, the patient achieved a complete response at day 90 based on RECIST criteria, which was confirmed by central review at day 180. Complete responses are rarely observed in solid tumor CAR T-cell studies, and none had previously been reported in lung cancer.
“It is exciting to share the first report of a complete response to CAR T-cell therapy in a patient with a hard-to-treat case of non-small cell lung cancer,” said Salman R. Punekar, M.D., assistant professor of medicine at NYU Langone Health, Perlmutter Cancer Center, and the treating physician. “These findings suggest that A2B694 may represent a new precision cell therapy approach for mesothelin-expressing solid tumors, if further studies continue to show positive results.”
As of September 11, 2025, nine patients had been treated in EVEREST-2 across three dose levels: 1×10⁸, 2×10⁸, and 4×10⁸ cells. The study includes patients with NSCLC, ovarian cancer, pancreatic cancer, colorectal cancer, gastro-esophageal cancer, and mesothelioma. The maximum tolerated dose has not yet been reached, and dose escalation continues, with higher doses of up to 14×10⁸ cells planned.
A2B694 has demonstrated manageable safety with no dose-limiting toxicities. Lymphodepletion prior to infusion resulted in expected, transient cytopenias. No cases of cytokine release syndrome were reported. One case of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred and was successfully managed. No deaths were attributed to treatment, and no patients discontinued due to adverse events.
Pharmacokinetic data show that A2B694 cells expanded in peripheral blood and were also detected in tumor tissue. In one case, the therapy was identified in a tumor biopsy at day 42 even when no circulating cells were detectable in blood, indicating that the therapy can infiltrate tumor tissue and persist within the tumor microenvironment.
Enrollment is ongoing and dose escalation is continuing.
