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Brief description/objective

While many men diagnosed with locally confined disease may be treated definitively with radiation or surgery, ap-proximately 30% of men have recurrent disease and go on to develop metastatic prostate cancer. In addition, 5% to 30% of men with prostate cancer have metastatic disease at initial diagnosis, a percentage that varies greatly by region, but is on an increasing trend that is expected to continue in the future [Cancer registration committee of the Japanese Urological Associa 2005] [Jack, R. H., et al 2010] [Scher, H. I., et al 2015] [Kelly, S. P., et al 2018] [Weiner, A. B., et al 2016] [Smith, S. 2018] [National Cancer Institute 2019].
Once prostate cancer has become metastatic there are no longer any curative treatments and expected median sur-vival is less than 5 years. Patients with metastases have traditionally been treated first with ADT, usually with LHRH agonist or antagonist that results in suppression of testos-terone production in the testes. This alone often succeeds in controlling disease for some time, years in many cases. However, prostate cancer progresses invariably and re-quires additional systemic therapies to re-establish control of disease.
Both docetaxel and abiraterone have been shown to prolong OS when combined up-front with ADT and are now considered standard of care for men diagnosed with high-volume or high-risk mHSPC. More recently, the second-generation androgen receptor inhibitors apalutamide and enzalutamide were examined in patients with mHSPC. Combination of apalutamide with ADT resulted in a signifi-cant improvement in both rPFS (HR = 0.48, p Both docet-axel and abiraterone have been shown to prolong OS when combined up-front with ADT and are now considered standard of care for men diagnosed with high-volume or high-risk mHSPC. More recently, the second-generation androgen receptor inhibitors apalutamide and enzalutamide were examined in patients with mHSPC. Combination of apalutamide with ADT resulted in a significant improvement in both rPFS
The combination of enzalutamide with ADT was studied in two Phase 3 studies; one compared to ADT alone and the second compared to ADT plus a first-generation anti-androgen. In the first study (ARCHES), the addition of en-zalutamide to ADT resulted in a significant improvement in rPFS (HR=0.39, p
While these therapies are initially effective, patients invari-ably succumb to their disease and the effectiveness of subsequent therapies diminishes after progression on the prior therapy. Thus, there remains a significant unmet need for novel therapies or combination regimens for patients with metastatic prostate cancer.