Phase 3 Randomized, Double-blind, Placebo-controlled Study of Apalutamide and Androgen Deprivation Therapy in High-risk Localized or Locally Advanced Prostate Cancer

The primary objective of this study is to evaluate whether treatment with **apalutamide** plus androgen deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in subjects with high-risk localized or locally advanced **prostate cancer** leads to an improvement in pathological complete response (pCR) rate and metastasis-free survival (MFS) based on conventional or PSMA PET imaging, compared to placebo plus ADT. This is clinically relevant as it aims to enhance treatment outcomes and potentially improve survival rates in patients with aggressive forms of prostate cancer.

The clinical trial involves a total of **1324 participants** diagnosed with **high-risk localized or locally advanced prostate cancer**. The study population is exclusively male, with an age range of 18 years and older. Participants were selected based on specific inclusion criteria, including a histologically confirmed diagnosis of adenocarcinoma of the prostate and a high-risk disease profile as defined by Gleason Sum Score and other clinical parameters. All subjects have an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not include a vulnerable population, and female subjects are not part of the study. Participants are required to have adequate organ function and be candidates for radical prostatectomy with pelvic lymph node dissection. Lifestyle considerations such as diet and physical activity are not specified, but participants must be able to adhere to the study's prohibitions and restrictions. The trial aims to evaluate the efficacy of treatment with apalutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT in improving pathological complete response (pCR) rate and metastasis-free survival (MFS).

The clinical trial is a **randomized, double-blind, placebo-controlled, Phase 3 study** designed to evaluate the efficacy of **apalutamide** in combination with androgen deprivation therapy (ADT) in subjects with high-risk localized or locally advanced **prostate cancer**. The primary objective is to assess whether this treatment regimen improves the pathological complete response (pCR) rate and metastasis-free survival (MFS) compared to placebo plus ADT. The trial is expected to run from March 22, 2019, to July 1, 2024, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histologically confirmed adenocarcinoma of the prostate, and adequate organ function. Following randomization, participants will receive either the investigational product or placebo, administered orally as a **film-coated tablet**. The study includes regular follow-up visits to monitor safety, efficacy, and adherence to the treatment protocol. These visits will involve assessments such as imaging and laboratory tests to evaluate the primary and secondary endpoints.

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience unacceptable toxicity, non-compliance with the study protocol, or if the investigator deems it in the participant's best interest. The expected length of participant involvement is approximately 13 months, including the treatment and follow-up periods. The study is conducted in accordance with ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **apalutamide**, an experimental medication identified by the product code JNJ-56021927. Apalutamide is provided in the form of a **film-coated tablet** and is intended for **oral use**. The specific dosage and frequency of administration are not detailed in the provided data, but the treatment period is specified to last up to 12 months. The active substance, apalutamide, is of chemical origin and is manufactured by Janssen-Cilag International N.V. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study includes the use of **androgen deprivation therapy** (ADT) as a non-experimental treatment. This therapy is administered via **subcutaneous use** and is classified under the ATC code L02AE, which corresponds to gonadotropin-releasing hormone analogues. The specific pharmaceutical form is denoted as PHF00243MIG. The ADT serves as a standard-of-care therapy in conjunction with the experimental medication to evaluate its efficacy in the study population.

Another component of the trial involves the use of a **tumour detection** agent, which is administered through **intravenous use**. The active substance is categorized under the ATC code V09I, specifically for tumour detection purposes. The pharmaceutical form and specific dosage details are not provided, but the administration is intended to assist in the evaluation of treatment outcomes through imaging techniques.

Additionally, the trial includes the use of **other hormone antagonists and related agents**, classified under the ATC code L02BX. These agents are also administered via **subcutaneous use** and are part of the androgen deprivation therapy regimen. The pharmaceutical form and specific dosage details are not specified, but they are integral to the therapeutic approach being evaluated in the trial.

The efficacy of the clinical trial will be assessed using two primary endpoints: the **pCR rate** and **MFS**. The **pCR rate** is defined in the pathology charter and will be assessed by a pathology blinded independent central review (BICR). The **MFS** (metastasis-free survival) will be evaluated based on conventional or PSMA PET imaging. This is defined as the time from randomization to the first occurrence of radiographic distant metastasis on conventional imaging (CT/MRI and bone scan) or PSMA PET imaging, pathologic finding of distant metastasis, or death from any cause, whichever occurs first. These endpoints will be measured and analyzed to determine the efficacy of apalutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT in subjects with high-risk localized or locally advanced prostate cancer.