Novel mRNA-LNP-Based Intratumoral Immunotherapy in Patients With Advanced Malignant Solid Tumors

A Phase 1/2a Clinical Study to Evaluate the Safety Tolerability, Pharmacokinetics, and Preliminary Efficacy of a Novel mRNA-LNP PMC2129G12-Based Immunotherapy in Patients With Advanced Malignant Solid Tumors

PMC2129G12 is an investigational intratumorally administered messenger RNA-lipid nanoparticle (mRNA-LNP) immunotherapy designed to enable localized, transient expression of a humanized EpCAM-targeted CD3-engaging bispecific antibody together with the immunostimulatory cytokines to kill tumors by recruited immune T cells.

This Phase 1/2a, open-label study is designed to evaluate the safety and tolerability of PMC2129G12 encoding humanized EpCAM-targeted CD3-engaging bispecific antibody together with the immunostimulatory cytokines administered by intratumoral injection in patients with EpCAM-positive advanced malignant solid tumors. Secondary and exploratory objectives include characterization of pharmacokinetics, pharmacodynamic immune effects, and preliminary antitumor activity. The study will provide critical information to support further clinical development of PMC2129G12 as a novel intratumoral immunotherapy for patients with advanced epithelial cancers.

Inclusion Criteria:

• Age >18 years
• Histologically or cytologically confirmed advanced or metastatic solid tumor refractory to standard therapy
• EpCAM expression ≥2+ intensity in ≥50% of tumor cells by central IHC
• At least one measurable lesion per RECIST v1.1 (≥2 cm) that is anatomically accessible for intratumoral injection
• ECOG performance status 0-1
• Life expectancy ≥3 months
• Adequate hematologic, hepatic, renal, and coagulation function
• Willingness to use effective contraception

Exclusion Criteria:

• Prior EpCAM- or CD3-targeted therapy
• Active autoimmune disease requiring systemic therapy
• Uncontrolled infection or significant cardiovascular disease
• Active or symptomatic CNS metastases requiring immediate local therapy. Patients with treated, stable CNS metastases may be eligible.
• Ongoing ≥Grade 2 toxicity from prior anticancer therapy
• Known hypersensitivity to study drug components
• Pregnancy or breastfeeding