Phase 1 dose escalation of ACM-CpG, a polymersome-delivered TLR9 agonist for advanced solid tumors after prior treatment with checkpoint inhibitor.

Abstract

TPS91 Background: ACM-CpG is a novel innate immune activator comprising of TLR9 agonist CpG7909 encapsulated within polymer vesicles (“polymersomes”). This formulation enhances in vivo immune activation compared with free CpG. ACM CpG is preferentially taken up by the myeloid compartment leading to myeloid specific and myeloid driven immune activation. In preclinical animal models, ACM-CpG induced tumor regression, durable antitumor immune memory, and growth inhibition of distal, non-injected tumors. Intramuscular administration also achieved tumor control on abscopal subcutaneous tumors. Based on these findings, a Phase I clinical trial (NCT06587295) was initiated at the National Cancer Centre Singapore to evaluate the safety and early efficacy signals of intramuscular ACM-CpG monotherapy in patients with advanced solid malignancies. Methods: This is a 3+3 dose-escalation study of ACM-CpG administered intramuscularly as monotherapy, weekly over the first 8 weeks then fortnightly from the 9th week onwards. Eligible patients had advanced cancers with prior clinical response to immune checkpoint inhibitors, either alone or in combination with chemotherapy with clinical progression of disease prior to enrolment on trial. Dose escalation was performed over 3 dose levels. Safety and clinical review was performed prior to each dosing. Scans were performed 4-weekly in the first 8 weeks then 8-weekly thereafter. Serial cellular and soluble changes of immune response in peripheral blood were profiled using mass CyTOF, multiplex cytokine assays (Luminex/Olink), IFN-γ ELISPOT, and single-cell RNA/TCR sequencing. Clinical trial information: NCT06587295 .