Phase 1 MSK‑TCR5 CD8α/β‑armored KRAS/HRAS/NRAS G12D TCR‑T therapy

This Memorial Sloan Kettering Cancer Center (MSKCC) investigator-initiated Phase 1, open-label, dose-escalation trial tests MSK‑TCR5—an autologous T‑cell receptor–engineered T‑cell product designed to recognize the RAS G12D neoantigen presented by HLA‑A11:01. The “armoring” concept is to enhance engineered T‑cell function/persistence beyond a standard TCR‑T approach by adding CD8 alpha/beta co-receptor support (i.e., strengthening recognition of the target peptide–HLA complex), with the goal of improving activity in solid tumors. The study enrolls adults with unresectable, advanced/metastatic solid tumors (including CRC and NSCLC cohorts described in the record) whose cancers harbor KRAS, HRAS, or NRAS G12D and who carry HLA‑A11:01, generally after at least second-line therapy (some parts require prior immune checkpoint inhibitor exposure and/or biomarker-defined subsets such as dMMR/MSI‑H). The intervention is MSK‑TCR5 given at escalating cell doses, aiming to establish safety and a recommended dose for expansion. Today’s care for these patients is tumor-specific systemic therapy (often immunotherapy and/or targeted therapy when eligible, otherwise sequential chemotherapy), and this trial explores a precision, HLA-restricted cellular therapy option for the RAS G12D population where durable options are limited beyond standard lines.