337 Intratumoral immune therapy for recurrent breast cancer with polyICLC, and tremelimumab combined with systemic durvalumab

Background Intratumoral (IT) cancer therapies may enhance T cell activation and tumor infiltration when combined with systemic checkpoint blockade. This approach improve treatment of advanced breast cancer, which is commonly resistant to immune therapy. Methods A multicenter basket-style trial ( NCT02643303 ) was performed in patients solid tumors, who received polyICLC IT 1mg x 6, then intramuscular (IM) 3, intravenous (IV) durvalumab 1500 mg q4W. Most were assigned cohorts also receiving tremelimumab: 10 or 75 IV. Goals assess tolerability clinical activity. Treated tumors evaluated for infiltrates on days (d) 0, 15, 29 by multiparameter immunofluorescence histology. strong signal response patients; thus, an expansion cohort enrolled. We report analysis that subgroup. Results Nineteen participants treatment-refractory recurrent median 4 prior lines therapy enrolled treated IV IT/IM polyICLC. Seventeen tremelimumab (15 IT, 2 IV). Common treatment-related AEs fatigue, injection site pain, chills. There one dose-limiting toxicity a participant IV, died severe hyponatremia (DLT) progressive disease. Objective responses (1 complete; partial unconfirmed)) observed 5 (26%), including 2/9 triple-negative (TNBC) 3/10 non-TNBC. Median OS longer those CR, PR, SD (not reached) vs. PD not evaluable (5 months): two responders remain alive at 34+ 40+ months. In injected there significant increases from d0 d29 numbers/mm2 CD8+ cells, CD20+ B mature dendritic cells (DC), macrophages, CD56+ NK antigen-experience (CD45RO), cytotoxic function (granzyme B), (ICOS1), proliferation (Ki67). expressing LAG3 TIM3 increased, as did PDL1+ stromal cells. no differences IDO, ARG1, CD39, CD73. Among objective response, all others, proportions intratumoral Ki67 increased (p < 0.04). Conclusions plus safe has activity TNBC The enhances effectors markers hypothesis-generating data warrant confirmatory studies. Clinical associated survival CD8 proliferation. Trial Registration Ethics Approval study been approval the institutional review boards each participating institution (Roswell Park Cancer Institute: STUDY 00000121/I291016; Mount Sinai School Medicine: IRB-17-01692; University Virginia: IRB # 19276; Cleveland Clinic: 18-694; Toledo: 300176; Dartmouth: STUDY00031630; Emory: IRB00099445). All give informed consent before enrolling participating. FDA