Phase 1/2a PMC2129G12 intratumoral mRNA-LNP encodes EpCAM×CD3 bispecific + cytokines

This Phase 1/2a, open-label, single-arm study from IntraAb evaluates intratumoral PMC2129G12, an mRNA–lipid nanoparticle designed to drive localized, transient tumor expression of a humanized EpCAM-targeted, CD3-engaging bispecific antibody plus immunostimulatory cytokines. Mechanistically, the EpCAM×CD3 bispecific is intended to physically bridge T cells (via CD3) to EpCAM-positive tumor cells to trigger T-cell–mediated killing, while the co-expressed cytokines aim to further activate immune cells within the tumor microenvironment. The trial’s main goals are safety/tolerability (TEAEs, DLTs, MTD) plus pharmacokinetics/pharmacodynamics and preliminary antitumor activity. Eligible patients have refractory advanced/metastatic solid tumors with EpCAM positivity defined as at least 2+ intensity in at least 50% of tumor cells by central IHC, and must have a measurable lesion accessible for injection. The key angle is a “local biologics factory” approach—using intratumoral mRNA to generate a T-cell engager (and cytokines) at the tumor site to potentially widen the therapeutic index versus systemic CD3 bispecifics; today’s care for these refractory epithelial cancers is tumor-specific sequencing of systemic therapies (targeted therapy when actionable, immunotherapy for selected tumors, cytotoxic chemo, and sometimes ADCs), and this explores whether localized immune redirection can add activity where standard options have been exhausted.