Phase 3 Randomized Study of BMS-986365 Versus Docetaxel or Androgen Receptor Pathway Inhibitors in Metastatic Castration-resistant Prostate Cancer

The primary objective of this study is to evaluate the efficacy of the investigational drug **BMS-986365** compared to the investigator's choice of therapy, which includes either Docetaxel or a second androgen receptor pathway inhibitor, in patients with **metastatic castration-resistant prostate cancer (mCRPC)**. The primary endpoint is the time to disease progression, which is clinically significant as it directly impacts patient management and treatment planning in mCRPC, a condition characterized by resistance to conventional hormonal therapies.

Secondary objectives include:

• Comparing BMS-986365 with the physician's selected treatment by assessing overall survival post-treatment initiation.
• Determining the optimal dose of BMS-986365 that offers the best benefit-risk profile, balancing cancer control with treatment tolerance.
• Evaluating the pharmacokinetics of BMS-986365 by measuring drug levels in the bloodstream.
• Assessing additional biological markers to determine the drug's efficacy.
• Evaluating the tolerance and impact of the study drugs on symptoms, overall health, and quality of life.

The clinical trial involves a total of **586 participants** diagnosed with **Metastatic Castration-resistant Prostate Cancer (mCRPC)**. The study population consists exclusively of **male subjects** aged **18 years or older**. Participants were selected based on the progression of their advanced prostate cancer, with evidence of metastasis confirmed through imaging techniques such as bone scans or CT/MRI scans. The trial does not include a vulnerable population. Participants have previously undergone treatments with medications like abiraterone, enzalutamide, apalutamide, or darolutamide. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The trial aims to evaluate the efficacy of a new medication, BMS-986365, compared to a physician's choice of treatment, by assessing the time to disease progression.

The clinical trial is designed as a **randomized**, open-label, adaptive study to evaluate the efficacy of BMS-986365 compared to the investigator's choice of therapy, which includes either **docetaxel** or a second androgen receptor pathway inhibitor, in participants with metastatic castration-resistant prostate cancer (mCRPC). The trial is structured in two parts and aims to assess the primary endpoint of radiographic progression-free survival (rPFS) as determined by a blinded independent central review. Secondary endpoints include overall survival (OS) to determine if BMS-986365 extends life expectancy compared to other treatments.

The trial is expected to commence recruitment on May 1, 2025, and conclude by January 19, 2029. Participants will be involved in the study for the duration of the trial, with the possibility of early termination if they experience significant adverse effects or if their disease progresses beyond a predefined threshold. The study will include an initial screening visit to confirm eligibility based on criteria such as age, disease progression, and prior treatment history with medications like **abiraterone** or **enzalutamide**. Follow-up visits will be scheduled to monitor the participants' response to treatment and to collect data on safety and efficacy. The end-of-study visit will occur at the conclusion of the participant's involvement, where final assessments will be conducted.

Participants will be randomly assigned to receive either BMS-986365 or the investigator's choice of therapy. The trial will not be blinded, allowing both participants and investigators to know the treatment allocation. The study will adhere to rigorous ethical standards, and participants will be monitored closely for any adverse events. The trial's adaptive design allows for modifications based on interim results, ensuring the most effective and safe treatment options are pursued. The trial's methodology is robust, with a focus on generating reliable data to inform future treatment strategies for mCRPC.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. The primary experimental medication is **BMS-986365**, a chemical compound provided in capsule form. It is administered orally, with a maximum daily dose and total dose amount set at 9999 units, although the specific unit of measurement is not specified. The treatment period is also capped at 9999 time units, with the exact duration unspecified. The medication is developed by Celgene Corporation and is identified by the sponsor product code BMS-986365.

Among the comparator treatments, **Abiraterone** is utilized, which is a chemical substance available in tablet form. It is administered orally, with a maximum daily and total dose amount of 9999 milligrams. The treatment period is similarly capped at 9999 time units. Abiraterone is not a pediatric formulation and is not classified as an orphan drug.

**Prednisolone** is another comparator treatment, also a chemical compound in tablet form. It is administered orally, with the same dosing and treatment period limitations as Abiraterone. Prednisolone is not a pediatric formulation and is not classified as an orphan drug.

**Enzalutamide** is included as a comparator treatment, available in both tablet and capsule forms. It is administered orally, with a maximum daily and total dose amount of 9999 milligrams. The treatment period is capped at 9999 time units. Enzalutamide is not a pediatric formulation and is not classified as an orphan drug.

**Prednisone** is another comparator treatment, provided in tablet form and administered orally. It shares the same dosing and treatment period limitations as the other comparator treatments. Prednisone is not a pediatric formulation and is not classified as an orphan drug.

**Docetaxel** is used as a comparator treatment in the form of a concentrate for solution for infusion. It is administered as a solution for infusion, with a maximum daily and total dose amount of 9999 milligrams per square meter. The treatment period is capped at 9999 time units. Docetaxel is not a pediatric formulation and is not classified as an orphan drug.

All medications in this trial are chemical in origin, and participant compliance with the dosing schedule is monitored throughout the study. The trial aims to compare the efficacy of BMS-986365 against the investigator's choice of therapy, which includes the aforementioned comparator treatments, in participants with metastatic castration-resistant prostate cancer.

The efficacy of the investigational product BMS-986365 in the clinical trial will be assessed primarily through the endpoint of **radiographic progression-free survival (rPFS)**, as determined by Blinded Independent Central Review (BICR). This endpoint evaluates the duration until disease progression is observed via radiographic imaging techniques, such as X-rays or scans. The secondary endpoint for efficacy assessment is **Overall Survival (OS)**, which measures the length of time participants survive while receiving BMS-986365 compared to other treatments selected by the investigators.