Background: Novel agents given prior to RP allows the study of drug effect(s) in primary human prostate cancer (PC), supporting future clinical study development. Pre-clinical and clinical data (mostly in setting of castration resistant PC) support PARP ± androgen inhibition as therapy for some patients (pt). We undertook a study of olaparib (O) ± degarelix (D) prior to RP. Methods: 20 evaluable (pre and post RP tissue available with 86% dose compliance) pt randomised 1:1 to O or O+D. Primary endpoint: measure PARP inhibition by IHC. Secondary endpoints were feasibility, safety, tolerability. Exploratory objectives: changes PSA, circulating tumour DNA & intra-tumoral immune cells. Men, due for RP, with high volume or aggressive PC, consented and were treated with O (300mg bd) 15 days ± D (240mg once), prior to RP. Diagnostic biopsy and RP tissue were collected. Adverse events (AE) were graded according to CTCAE v4 and followed up to resolution or 6-weeks post RP. Results: 24 men recruited, 4 not evaluable (opted radiotherapy, surgery date altered, not by AE). Interim results are presented of available data. Conclusions: 2 weeks of O (± D) can be given prior to RP with acceptable safety profile. Exploratory analyses of tumour tissue are ongoing however, preliminary data confirm PSA drop noted for pt on both regimens. While expected for O+D this is the first report of PSA changes following a short course of single agent PARPi (O) in pt with local/ hormone sensitive PC. Clinical trial information: NCT02324998

Majority of related AEs Grade (Gr) 1, none > Gr 2. Commonest AE were O: fatigue, nausea & vomiting, O+D: injection site reaction, fatigue & nausea. No RP were delayed by AE. PSA declined from baseline in 8/8 pt O+D and 3/9 (11, 17 & 47%) pt O. Biomarker analysis are ongoing.