A randomized phase Ib/II study of nivolumab with or without BMS-986253 in combination with a short course of ADT in men with castration-sensitive prostate cancer (MAGIC-8).

TPS329 Background: Androgen deprivation therapy (ADT) is highly effective in castration-sensitive prostate cancer (CSPC) but is associated with significant side effects. Novel strategies to reduce ADT exposure and prolong disease control are needed. ADT initially induces a complex immune infiltrate within prostate tumors, suggesting that immunologic intervention may be more effective at the time of castration. Emerging data suggests that the cytokine interleukin-8 (IL-8) recruits immunosuppressive polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment (TME) of many malignancies, including prostate cancer and serum IL-8 levels correlate with lack of response to anti-PD-1 therapy. We hypothesize that immunotherapy with nivolumab (a PD-1 inhibitor) with or without BMS-986253 (an IL-8 inhibitor) combined with degarelix (an LHRH antagonist) will be safe and promote an anti-tumor immune response that can prolong time to disease relapse in CSPC. Methods: This is a randomized, multicenter, two-arm, phase 1b/2 trial of patients with biochemically-recurrent or low volume metastatic CSPC and a rapidly rising PSA (≤12 months). 60 patients will receive immunotherapy with nivolumab or nivolumab plus BMS-986253 for 24 weeks. 16 weeks of ADT with degarelix will be added after 8 weeks of immunotherapy alone. The primary endpoints are safety and PSA relapse rate 10 months after the initiation of therapy. Secondary endpoints include relapse-free survival (RFS), time to testosterone recovery, rate of metastatic progression and change in PSA with immunotherapy alone. Correlative studies will quantify the systemic immune response through cytokine analysis and peripheral T cell profiling using serum and whole blood specimens collected from all enrolled patients. Pre- and on-treatment biopsies will also be obtained from the subgroup of patients with metastatic disease to further define changes in the TME using RNA-sequencing and quantitative multiplex immunofluorescence. The study is open with 1 patient currently enrolled at the time of submission. Clinical trial information: NCT03689699.