1047P - AXA-042, a systemically administered TLR2/6 agonist, demonstrates target engagement and TLR pathway activation in patients with advanced solid tumors

Background

AXA-042 is a novel synthetic, pegylated toll-like receptor (TLR) 2/6 agonist in development for the treatment of advanced solid tumors. Nonclinical pharmacology studies have demonstrated that AXA-042 functions through a multicellular mechanism, including activation of the pro-inflammatory innate immune response, reduction in immunosuppressive macrophages at the tumor site, activation of dendritic cells, and release of chemokines to facilitate T-cell recruitment. A first-in-human study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AXA-042 as monotherapy and in combination with a checkpoint inhibitor in subjects with advanced solid tumors is currently ongoing (ACTRN12622000993796).

Methods

AXA-042 is administered intravenously once every 21 days. After obtaining informed consent, whole blood and plasma samples were collected from patients pre- and post-treatment for assessment of AXA-042 pharmacokinetics and pharmacodynamic biomarkers. The Nanostring nCounter™ PanCancer IO 360 Panel and a 43-marker CYTOF panel were used to identify AXA-042 transcriptomic and immune modulation response signatures in whole blood samples collected 24- and 168-hours post dose. The OLINK Target 48 Cytokine Panel was used for the longitudinal assessment of cytokine modulation.

Results

Preliminary statistical analysis of immunomodulatory effects pre- and post- treatment is consistent with the proposed mechanism of AXA-042. Samples from the initial cohort of patients (n=3-6) displayed consistent transient induction of cytokines and chemokines, that returned to baseline within 2-8 hours post dose. Nanostring analysis confirmed TLR pathway engagement and revealed an induction of pro-inflammatory gene signatures, associated with myeloid cell activation and NFkB signaling. CYTOF characterization of immune subset activation and additional transcriptomic analyses are underway and will be presented.

Conclusions

AXA-042 demonstrates on-target biological activity in patient blood samples. Further biomarker analyses are ongoing and will be correlated with clinical activity in a larger number of patients.

Clinical trial identification

ACTRN12622000993796.

Editorial acknowledgement

Legal entity responsible for the study

Axelia Oncology.

Funding

Axelia Oncology.

Disclosure

A. Latifi, P. Kearney: Financial Interests, Personal, Full or part-time Employment: Axelia Oncology. P. Wabnitz, A. Galkin: Financial Interests, Personal, Financially compensated role: Axelia Oncology. All other authors have declared no conflicts of interest.