Optimal PSA Triggered Individual Management of Androgen Sensitive Prostate Cancer

Inclusion criteria

Cohort A Eligibility (Step 1 Registration)

• Participant aged ≥ 18 years
• Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology.
• Metastasis detected any time prior to study registration on conventional or functional imaging as determined by the treating investigator and can be of any site.
• Baseline testosterone >50 ng/dl before start of therapy for metastatic disease
• PSA ≥ 1 ng/mL before start of therapy for metastatic disease
• ECOG Performance Status ≤ 2
• Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator.
• Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1.

• If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2.
• Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy.
• Clinically significant adverse effects from any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy) must have resolved or have been determined to be clinically stable per the Investigator.
• Has access to a smartphone and wireless services and is able to download and navigate study specific applications.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Cohort A Eligibility (Step 2 Registration) -PSA ≤ 0.2 ng/mL after 6-12 months of relugolix and androgen receptor pathway inhibitor treatment. Androgen receptor pathway inhibitor includes abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs.

Cohort B Eligibility

• Participant aged ≥ 18 years
• Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology.
• Metastasis detected any time prior to study registration on conventional or functional imaging as determined by clinical investigator and can be of any site.
• PSA ≤ 0.2 ng/mL after treatment with androgen deprivation therapy or androgen receptor pathway inhibitor treatment or both of any duration. Androgen deprivation therapy in this context includes gonadotropin-releasing hormone agonists and antagonists. Androgen receptor pathway inhibitors include abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs.
• Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator.
• Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1.

• If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2.
• Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy.
• Has access to a smartphone and wireless services and is able to download and navigate study specific applications.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion criteria

Cohort A Eligibility (Step 1 Registration)

• Participant received androgen deprivation therapy (defined as leuprolide or surgical castration) for metastatic hormone-sensitive prostate cancer.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Known brain metastases or cranial epidural disease.

--Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry.

• Current evidence of uncontrolled, significant intercurrent illness, infection, non-compliance or other safety concerns which may affect clinical trial participation.
• Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3).
• Participants taking prohibited medications as described in Section 6.6.2.

Cohort A Eligibility (Step 2 Registration)

• Receiving other systemic anti-cancer therapy for prostate cancer. Prior treatment before Step 2 registration is allowed.
• Progression to metastatic castration-resistant prostate cancer per clinical investigator.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Participants taking prohibited medications as described in Section 6.6.2.

Cohort B Eligibility

• Receiving other systemic anti-cancer therapy for prostate cancer.
• History of surgical castration.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Known brain metastases or cranial epidural disease.

--Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry

• Current evidence of uncontrolled, significant intercurrent illness, infection, compliance or other safety concerns which may affect clinical trial participation.
• Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3).
• Participants taking prohibited medications as described in Section 6.6.1.