Background: The long-standing approach to mCRPC management has been to treat sequentially with one agent until resistance is met. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non–cross-reactive regimen as a way to more effectively treat an intrinsic heterogeneous disease, delay or prevent drug resistance, and minimize treatment toxicity. Methods: All patients receive treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks. Upon completion of regimen, patients are followed on ADT alone. Primary endpoint for the study is time to progression (TTP), either by PSA or imaging. Secondary endpoints are PSA response rate with each module, changes to alkaline phosphatase levels, and safety. Results: From 3/2017 to 11/2020, 40 men with mCRPC were enrolled, with 33 completing the 9-month study regimen and evaluable for endpoint analysis. With median follow up of 139 weeks, median TTP after regimen completion was 15.9 weeks (95% CI 10.6-25.0 weeks), which did not meet prespecified TTP of 20 weeks to be considered a significant improvement over standard management. PSA response rates showed successive improvement with each sequential treatment module (Table). 77.8% of patients with elevated baseline alkaline phosphatase levels had normalization post-treatment. Previously reported, the treatment regimen was well-tolerated, with few grade 3/4 AE’s attributable by the investigator to the study regimen. Five patients (15.2%) were able to remain on post-study surveillance with ADT alone without the addition of a mCRPC agent for over a year, with one patient subsequently discontinuing ADT with PSA remaining undetectable in setting of recovering testosterone levels. Conclusions: Treatment of mCRPC with a rapidly cycling non–cross-reactive regimen did not significantly improve time to disease progression as compared to standard management. However, it is associated with significant antitumor response, with potential for long-term suppression of disease. Additional analysis into clinicopathologic and genomic factors that may predict for prolonged disease control is ongoing. Clinical trial information: NCT02903160.