Using G100 (Glucopyranosyl Lipid A) to transform the sarcoma tumor immune microenvironment.

11017Background: Tumor associated macrophages (TAM) are critical for immune evasion in many tumors. We hypothesized that combining G100, a TLR4 agonist that stimulates innate immunity and increases inflammation preclinically, with radiation (rads) would drive TAM to an M1 phenotype, creating a strong T-cell response. Methods: We began an investigator-sponsored, phase I study for patients (pts) with met. sarcoma and a tumor safely injectable in an outpt clinic. We treated two, 6 pt cohorts with 5 or 10 mcg G100 in 8 weekly intra-tumor (IT) injections. Rads was given to the injected tumor at a dose of 30 + Gy in <5 fractions. Pre and post treatment biopsies were required. Results: 12 pts were enrolled; each cohort accrued in less than 3 months demonstrating feasibility of IT injection sarcoma trials. Sarcoma subtypes included: 6 pts with leiomyosarcoma (LMS), 2 with synovial and 1 each with myxofibrosarcoma, chondrosarcoma, epithelioid and undifferentiated round cell sarcoma (URCS). Pts had a median of 3 pr...