Evaluating Autologous Logic-gated Tmod CAR T-Cell Therapy Targeting Mesothelin in Adults with Advanced Solid Tumors Showing HLA-A*02 Loss

What this Trial Is About

Researchers are evaluating autologous logic-gated Tmod CAR T-cell therapies in adults with recurrent, unresectable, locally advanced, or metastatic solid tumors expressing mesothelin MSLN and having lost HLA-A*02 expression. The study includes several cancer types such as colorectal, pancreatic, non-small cell lung, ovarian, mesothelioma, and others. This phase 12 trial aims to find a safe and effective dose and assess the therapys ability to target tumor cells while protecting healthy cells. Participants receive T cell collection in a pre-screening study, followed by a preconditioning lymphodepletion regimen before receiving a single intravenous dose of one of two investigational CAR T-cell products A2B694 or A2B543. The study has two arms, each investigating one of these products. The phase 1 portion focuses on safety and dose optimization, while phase 2 evaluates further safety and efficacy. During the study, participants undergo various assessments including tissue analysis, imaging to measure tumor lesions, and laboratory testing. Researchers will monitor adverse events, dose limiting toxicities, and treatment responses over up to 24 months post-infusion. Additional analyses include persistence of the CAR T cells and cytokine levels. Participants are followed long-term to evaluate safety and treatment impact, with total involvement lasting up to two years after infusion.

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