Background: Adenosine, generated by the ectonucleotidase CD73, mediates immunosuppression within the tumor microenvironment by triggering adenosine 2A receptors (A2AR) on immune cells. Tumor CD73 expression may be prognostic in prostate cancer. We evaluated the clinical activity of adenosine blockade using A2AR antagonist, ciforadenant, with or without the anti-PDL-1 antibody, atezolizumab (atezo), in advanced mCRPC patients (pts) in an ongoing phase 1 trial. Methods: Eligibility required measurable disease and up to 5 prior systemic therapies. Prior anti- PD-(L)1 was allowed. Ciforadenant was administered orally BID as monotherapy at 50-200mg or 100mg in combination with atezo 840mg IV Q 2 weeks (wks). Safety and efficacy were evaluated by CTCAE4, RECIST1.1 and PCWG2. Serum was obtained for measurement of cytokines. Results: Of 33 enrolled pts, 10 received ciforadenant monotherapy and 23 in combination with atezo. As of 10/21/19, 14 pts are evaluable for response and described further. Median prior therapies is 3 (range 2-6) with median follow-up 10.8 (4-33) wks. Metastatic burden included 4 node only, 2 bone plus node, and 8 visceral metastases. Five pts experienced tumor regression: 2 ciforadenant monotherapy (tumor reductions 12%, 17%); and 3 combination (tumor reductions 4%, 27%, 42%). The pt with a partial response had PSA decline from 98 ng/mL to <1. Eight pts had stable disease (SD) for a clinical benefit rate (SD + PR) of 8/14 (57%). Median duration of disease control was 24 wks. Study treatment was well tolerated with two Gr3/4 adverse events (AEs) of fatigue (1) and anorexia (1). The most common Gr1/2 AEs were fatigue and nausea. Serum TNFα levels increased by 4-8 wks on therapy in 12/13 pts. Baseline levels of soluble VCAM-1, which has been implicated in metastatic spread/more aggressive disease, were higher in pts with tumor regression (771 ± 109 ng/mL, n=4) than pts with tumor growth (544 ± 62 ng/mL, n=5, p<0.05). Conclusions: Results from this phase 1 study show mCRPC can be sensitive to A2AR blockade with ciforadenant. Cytokine changes provide evidence of treatment-induced inflammatory response, which may predict efficacy. Data on all 33 enrolled pts will be presented. Clinical trial information: NCT02655822