Satraplatin (DB04996): A Comprehensive Monograph on a Novel Oral Platinum Agent

Executive Summary

[Satraplatin (DB04996) emerged as a scientifically compelling fourth-generation, orally bioavailable platinum(IV) analogue designed to overcome the limitations of intravenous administration and the resistance mechanisms associated with earlier platinum agents. Preclinical and early clinical data demonstrated significant antineoplastic activity and a favorable safety profile, notably lacking the nephro-, neuro-, and ototoxicity of cisplatin. The pivotal Phase III SPARC trial in metastatic castrate-refractory prostate cancer (mCRPC) successfully met its primary endpoint of improving progression-free survival (PFS). However, it critically failed to demonstrate a corresponding benefit in the co-primary endpoint of overall survival (OS). This discordance between PFS and OS became the central, insurmountable hurdle in its regulatory review, leading to unanimous negative recommendations from advisory committees and the eventual withdrawal of marketing applications in both the United States and Europe. The story of Satraplatin serves as a seminal case study on the importance of endpoint selection in oncology trials and the high bar of demonstrating a clear survival benefit for regulatory approval in the modern era.]

1.0 Introduction: The Quest for an Oral Platinum Antineoplastic Agent

1.1 The Unmet Need in Platinum-Based Chemotherapy