A2 Bio presented progress on its Tmod™ CAR T-cell clinical programs at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting, highlighting advancements in its dual-receptor CAR T-cell therapies for challenging cancers. The Tmod™ platform addresses on-target, off-tumor toxicity by targeting two or more antigens for selective tumor killing, while protecting normal cells via a blocker that recognizes antigens expressed only on normal tissues.
BASECAMP-1 Prescreening Study
The BASECAMP-1 study, an ongoing nationwide prescreening initiative, utilizes next-generation sequencing (NGS) from Tempus AI to identify participants with tumor-associated HLA-A*02 LOH, making them eligible for Tmod™ CAR T-cell therapy trials. As of September 1, 2024, 70 participants have been enrolled. An amendment to eligibility criteria based on Tmod™ blocker data has led to potential enrollment increases of 16% for Hispanic, 43% for African American, and 112% for Asian and Pacific Islander participants, enhancing trial diversity.
Julian R. Molina, M.D., Ph.D., professor of oncology, Mayo Clinic, noted that the data from BASECAMP-1 will enable more efficient patient identification and enrollment across leading academic centers in the United States.
EVEREST-1 Clinical Trial
EVEREST-1 (NCT05736731) is a Phase 1/2 study evaluating the safety and efficacy of A2B530, a Tmod™ CAR T-cell therapy targeting carcinoembryonic antigen (CEA) in adults with recurrent, unresectable, locally advanced, or metastatic non-small cell lung, colorectal, pancreatic, or other CEA-expressing solid tumors. As of September 1, 2024, 14 patients have been enrolled, including four with pancreatic cancer and 10 with colorectal cancer. Two pancreatic cancer patients have reached one-year survival post-infusion.
Pharmacokinetic data from 14 patients suggest a potential dose-response relationship, with higher doses correlating with increased Tmod™ cell expansion. No dose-limiting toxicities, grade >3 serious adverse events, or neurotoxicity related to A2B530 have been reported. Dose escalation is ongoing, and the maximum tolerated dose has not yet been reached. Patrick M. Grierson, M.D., Ph.D., assistant professor at Washington University in St. Louis, shared these safety and early biomarker data.
EVEREST-2 Clinical Trial
EVEREST-2 (NCT06051695) is a Phase 1/2 study assessing the safety and efficacy of A2B694 in adult patients with solid tumors. A2B694 targets mesothelin (MSLN). The first patient was enrolled in April 2024, and dose escalation is ongoing.
About the Tmod™ Platform
The Tmod™ platform utilizes a dual-receptor system, comprising an activator and a blocker, to selectively target and kill tumor cells while protecting normal cells. The activator recognizes antigens on tumor cells, triggering their destruction, while the blocker recognizes antigens on normal cells, preventing their harm. This approach aims to provide precise, personalized, and effective T cell targeting in cancer therapy.
