Background: A phase I study of Cabozantinib (C) in combination with docetaxel (D) and prednisone (P) in patients (pts) with mCRPC determined that 40 mg daily was the maximum tolerated dose of C in combination with D and P (C+DP). We report a pooled analysis of the phase I and randomized phase II study comparing C+DP to DP alone. Methods: Eligible pts had mCRPC without prior chemotherapy in the castrate setting. All pts received a fixed dose of D (75 mg/m²IV day one of each 21 day cycle) and P (5 mg PO twice daily), and in the C+DP group, C at three escalating dose levels: 20 mg, 40 mg, or 60 mg in the phase I cohort (all PO daily) and 40 mg daily in the phase II cohort. Results: A total of 32 pts received C+DP (19 pts in phase I and 13 pts in the phase II cohort). 12 pts received DP alone. Baseline characteristics for C+DP vs DP included median age 69 (45 – 84) vs 69 (50-83) and median PSA 74.8 ng/ml (0.01-4093.7) vs 309.5 ng/ml (94.6 – 2649) respectively. Clinical trial information: NCT01683994 18/32 C+DP pts had previous enzalutamide or abiraterone, with a median PFS of 13.6 months (95% CI: 5.2 – 21.0). 23/32 pts (72%) treated with C+DP required dose reduction or discontinuation of C, and 10/32 (31%) required C discontinuation. 2/32 patients (6%) in the C+DP group died on protocol, possibly related to study drug (sudden death NOS/venous thromboembolism). Grade 4 adverse events (AEs) in the C+DP group included: neutropenia (28%), leukopenia (6%), pulmonary embolism (3%), and mucositis (3%) and in DP: hyperglycemia (8%). Grade 3 AEs (>10%) in C+DP included: neutropenia (31%), febrile neutropenia (16%), leukopenia (13%), hypophosphatemia (13%) and in DP: anemia (17%). Conclusions: In pts with mCRPC, C+DP is associated with a greater PFS and PSA responses compared to DP alone. Toxicities with the combination were manageable. Further study is required to better define the potential benefits of C+DP in mCRPC.