Phase 1 ACM-CpG TLR9 agonist polymer-lipid nanoparticle for peritoneal metastases

This Phase 1, open-label, dose-escalation study (standard 3+3) tests escalating intraperitoneal injections of ACM-CpG to define safety, dose-limiting toxicities, and the maximum tolerated dose/optimal biologic dose in patients with inoperable peritoneal metastases or malignant ascites from colorectal or appendiceal adenocarcinoma. ACM-CpG is a Toll-like receptor 9 (TLR9) agonist CpG oligonucleotide formulated in a polymer-lipid nanoparticle (“polymersome”-style) intended to activate innate immunity (notably plasmacytoid dendritic cells) and drive downstream anti-tumor T-cell priming within the peritoneal compartment. Participants receive at least one injection on Day 1 of a 28-day cycle, with up to two additional injections allowed for stable/responding disease, and imaging every 8 weeks initially. The sponsor is Brown University (Brown University Health at Rhode Island Hospital/Miriam Hospital), and the drug platform is associated with ACM Biolabs, giving this academic-led peritoneal delivery trial a translational angle: testing whether local innate immune activation can improve outcomes where today’s care is systemic chemotherapy/targeted therapy (and immunotherapy only for select molecular subsets) plus symptomatic drainage/supportive care for ascites, with cytoreductive surgery/HIPEC reserved for operable candidates.