(P 440) CASE REPORT: COMPLETE CLINICAL AND MOLECULAR RESPONSE TO INTRATUMORAL STX-001, AN LNP-SELF REPLICATING MRNA EXPRESSING IL-12 IN A PATIENT WITH REFRACTORY ANGIOSARCOMA

Objective: Angiosarcoma (AS) is a rare, aggressive malignancy affecting the vascular and lymphatic system with limited treatment options and poor prognosis. We report a patient with refractory AS who achieved complete clinical and molecular response following intratumoral (IT) injection of STX-001, a lipid nanoparticle (LNP) encapsulated self-replicating mRNA encoding interleukin-12 (IL-12). STX-001 has a unique mechanism of action: it induces LNP-triggered immunogenic cell death, while its self-replicating mRNA activates pattern-recognition receptors via nucleic acid sensing, and drives IT IL-12 to levels multiple logs higher, and with longer duration, than previous generations of IL-12-based therapeutics.

Methods: A 70-year-old female patient (pt) presented with AS on the left chest. Previous biopsy had high-grade atypical vascular proliferation with CD31, CD34, and MYC amplification, consistent with radiation-induced AS due to prior breast cancer treatment. Prior therapies for AS included surgical resection, pazopanib, paclitaxel, and gemcitabine+docetaxel. Pt was enrolled in the monotherapy STX-001 dose escalation clinical trial (NCT06249048), receiving 300 µg of STX-001 once every 3 weeks.

Results: The pt had transient adverse events of grade 3 neutropenia and liver enzyme elevation, and grade 1 cytokine release syndrome. Radiographic assessment demonstrated partial response by RECIST criteria on day 207 after initial STX-001 injection. Day 10 on-treatment biopsy revealed reduced cellularity with evidence of degeneration, necrosis, and immune infiltration, as well as a 3x rise in CD4 and 25x rise in CD8 T cells from baseline (quantified by immunohistochemistry). Biopsies on Days 56 and 190 demonstrated a complete pathological response, increased T cell infiltration, and PD-L1 expression. Baseline plasma ctDNA was at 0.82 MTM/ml and on day 230 was undetectable.

Conclusion: This case demonstrates preliminary activity of STX-001 in refractory AS with the potential to induce a T cell infiltrated tumor microenvironment. STX-001 may offer a promising strategy for sarcomas refractory to conventional treatments.