A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products in Adults With Advanced Solid Tumors Expressing MSLN and Lost HLA-A*02 Expression

What this Trial Is About

Researchers are evaluating autologous logic-gated Tmod™ CAR T-cell treatments in adults with certain solid tumors such as colorectal, pancreatic, non-small cell lung, ovarian cancers, mesothelioma, and other tumors that express mesothelin and have lost HLA-A*02 expression. This phase 1/2 study aims to find a safe dose and examine whether the treatment can kill tumor cells while protecting healthy cells. The study includes patients with recurrent unresectable, locally advanced, or metastatic disease who have already enrolled in a related pre-screening study for T cell collection. Participants receive a preconditioning lymphodepletion regimen followed by a single intravenous infusion of one of two experimental Tmod CAR T-cell products, A2B694 or A2B543. The study has two arms, each testing one of these products after the lymphodepletion. T cells are collected and stored in a prior study, then manufactured and infused when the participant progresses in their disease. There is no required waiting period between the pre-screening and treatment studies. During the study, participants will undergo regular assessments including monitoring for adverse events and dose-limiting toxicities up to 24 months after infusion. Researchers will measure the recommended dose by 21 days post-infusion and overall response rate at 24 months. Additional evaluations include persistence of the CAR T cells and cytokine analysis. Participants are expected to comply with study procedures and long-term safety follow-up throughout the study period.

A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression