Sequential Therapies ("First Strike, Second Strike") for the Treatment of High-Risk Metastatic Castration-Sensitive Prostate Cancer

Inclusion Criteria

• Biopsy proven prostate cancer and the diagnosis can be established through either prostate biopsy or biopsy of a metastatic lesion. High risk mCSPC is defined as having 2 of the 3 risk factors: a Gleason score of 8 or more, at least 3 bone metastases, and the presence of measurable visceral metastasis.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• No androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) analogue monotherapy for more than 12 weeks after the diagnosis of metastatic prostate cancer. Prior ADT in the non-metastatic setting is allowed if it was given > 2 years prior to the diagnosis of metastatic prostate cancer and a reduction of prostate specific antigen (PSA) is documented after initiating ADT in the metastatic setting.
• Agreeable to prostate biopsy after completing “second strike".
• Absolute neutrophil count > 1000/l
• Hemoglobin (Hb) > 10 g/dl
• Platelet > 100,000/l
• Creatinine and liver enzymes within 1.5 folds of upper limits of normal
• No uncontrolled arrhythmia; patients with history of (h/o) myocardial infarction or history of congestive heart failure, need to have estimated left ventricle ejection fraction above 40% either on echocardiogram or multi-gated acquisition (MUGA) scan within 6 months of study enrollment.
• All men who are sexually active with a female partner of childbearing potential treated or enrolled on this protocol must agree to use highly effective barrier contraception prior to the study, for the duration of study participation, and for 7 months after last dose of tislelizumab administration.
• Ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the subject's behalf. Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria

• Prior treatments with TAK-700/Orteronel, abiraterone, darolutamide, apalutamide or enzalutamide for more than eight weeks.
• Any previous treatment with a PD-1 or PD-L1 inhibitor.
• Documented brain metastases.
• Prior prostatectomy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel (including any drugs formulated with polysorbate 80), or LHRH analogue (e.g., leuprolide, triptorelin, goserelin acetate, degarelix).
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs.
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy & have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with delayed healing of wounds, ulcers, and/or bone fractures.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for tislelizumab to be less clinically active in this population.
• Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., Crohn’s disease), systemic lupus erythematosus, Sarcoidosis syndrome, Grave’s disease, rheumatoid arthritis, hypophysitis, uveitis, with the following exceptions: * Vitiligo or alopecia * Hypothyroidism stable on hormone replacement * Chronic skin condition that does not require systemic therapy * Celiac disease controlled by diet alone * Participants with inactive disease in the last 5 years may be included.
• Active infection including tuberculosis, hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants with positive HCV antibody are eligible if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
• Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study chemoimmunotherapy, with the following exceptions: premedication for docetaxel with 8 mg oral dexamethasone approximately 12 hours (hr), 8 hr and 1 hr prior to each docetaxel administration; intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection); systemic corticosteroids at physiologic doses not exceeding 10mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before computed tomography [CT] scan).
• History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
• Was administered a live vaccine =< 4 weeks before first dose of tislelizumab. Note: Seasonal vaccines for influenza and COVID-19 vaccines are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Inability to comply with protocol requirements.