Background: BIND-014 is a novel PSMA-targeted Accurin (polymeric nanoparticle) that contains docetaxel (D). BIND-014 is anticipated to improve the therapeutic index of D by increasing its intratumoral concentration and duration of exposure. In a phase 1 study, BIND-014 was generally well-tolerated and displayed anti-tumor effects, including in two patients with chemotherapy-naïve mCRPC. Methods: A phase 2 study was conducted of BIND-014 administered by a 60-min IV infusion at 60 mg/m² on day 1 of a 21-day cycle in combination with 5 mg of prednisone twice per day to patients with chemotherapy-naïve mCRPC. Prior treatment included abiraterone acetate (AA, 48%), enzalutamide (E, 12%) or both (14%). Of these 31 patients 19% progressed within ≤ 6 months on prior AA and/or E. The primary endpoint was radiographic progression-free survival (rPFS) using PCWG2 for bone and RECIST v1.1. Other endpoints included prostate specific antigen (PSA) and circulating tumor cell count (CTC) conversions, objective response rate (ORR), and overall survival (OS). Results: Forty-two patients were enrolled and received a median of 6 doses (range 1 – 21). Median rPFS was 7.1 months (95% CI: 2.6 – 9.9) with 4 patients (10%) censored. PSA response ( ≥ 50% reduction from baseline) was observed in 12 of 40 patients (30%). CTC conversions (from ≥ 5 CTCs/7.5 mL of blood at baseline to < 5 CTCs) occurred in 13 of 26 patients (50%). ORR was 32% with 3 confirmed responses (1 complete response and 2 partial responses) and 3 unconfirmed responses out of 19 patients with measurable disease. Estimated median OS was 13.4 months (95% CI: 9.9 – 18.6) with 14 patients (33%) censored. The most common hematological treatment-related adverse events (TRAEs) observed were lymphopenia (26%), and anemia (19%).Fatigue (69%), nausea (55%), diarrhea (45%), dyspnea (36%), and neuropathy (33%) were the most common non-hematological TRAEs. The most common TRAEs were generally grade 1 and 2. Conclusions: BIND-014 administered at 60 mg/m² on day 1 of a 21-day cycle is clinically active and well-tolerated when administered to patients with chemotherapy-naïve mCRPC including those with prior AA and/or E. Clinical trial information: NCT01812746