For patients with metastatic castration-resistant prostate cancer (mCRPC), the development of new therapeutic options is a crucial step forward. BMS-986365, an investigational oral drug, has shown promising results in preclinical and early clinical trials, and now it has entered a pivotal Phase 3 study, with recruitment starting in March 2025 at 230 locations across the world.

BMS-986365 stands out for its innovative dual mechanism of action. It targets the androgen receptor (AR), a key driver of prostate cancer progression, by both degrading the receptor and antagonizing its activity. This dual approach not only suppresses AR signaling but also tackles mutated forms of the receptor, which are often responsible for resistance to conventional therapies. Preclinical studies demonstrated significant tumor growth inhibition, providing a strong foundation for its clinical development.

Earlier-phase clinical trials showed encouraging outcomes. Patients who had exhausted other treatment options, including existing androgen receptor pathway inhibitors, experienced measurable responses to BMS-986365. In a first-in-human study, up to 70% of patients at the highest dose saw a PSA decline of 30% or more, a key marker for prostate cancer progression. Additionally, the drug was well tolerated, with manageable side effects, and demonstrated a median radiographic progression-free survival of 6.3 months, a significant result for heavily pretreated patients.

Now, in its Phase 3 trial, BMS-986365 is being evaluated on a global scale. This trial aims to confirm its efficacy and safety in a broader patient population. With recruitment open at 230 sites across multiple countries, the study reflects the worldwide demand for innovative therapies in advanced prostate cancer. The trial will include men with mCRPC who have previously been treated with standard-of-care therapies, such as androgen receptor inhibitors or chemotherapy.

If successful, BMS-986365 could offer new hope to men facing the most advanced and resistant forms of prostate cancer. Its ability to degrade and antagonize the androgen receptor directly addresses one of the major drivers of resistance in this disease, potentially improving outcomes where other therapies fall short.

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