Eine randomisierte, doppelblinde Phase-3-Studie mit Pembrolizumab oder Placebo in Kombination mit Enzalutamid und einer Androgen-Suppressionstherapie in Patienten mit metastasiertem, hormonsensitivem Prostatakrebs (KEYNOTE-991).

Biological: Pembrolizumab;Drug: Enzalutamide;Drug: Androgen Deprivation Therapy (ADT);Other: Placebo

Gender: Male
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- Male participants with histologically- or cytologically-confirmed adenocarcinoma of
the prostate without small cell histology

- Has metastatic disease assessed by investigator and verified by BICR by either =2 bone
lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance
imaging (CT/MRI)

- Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a
luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study
treatment or have a history of bilateral orchiectomy

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed
within 10 days of randomization

- Participants receiving bone resorptive therapy (including, but not limited to,
bisphosphonate or denosumab) must have been on stable doses prior to randomization

- Has adequate organ function

- Has provided newly obtained core or excisional biopsy (obtained within 12 months of
screening) from soft tissue not previously irradiated (samples from tumors progressing
in a prior site of radiation are allowed). Participants with bone only or bone
predominant disease may provide a bone biopsy sample

- Male participants must agree to the following during the intervention period and for
at least 120 days after the last dose of study intervention: Refrain from donating
sperm PLUS either be abstinent from heterosexual intercourse and agree to remain
abstinent OR agree to use contraception, unless confirmed to be azoospermic

- Male participants must agree to use male condom when engaging in any activity that
allows for passage of ejaculate to another person of any sex

Exclusion Criteria:

- Has a known additional malignancy that is progressing or has required active treatment
in the last 3 years

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

- Has undergone major surgery including local prostate intervention (excluding prostate
biopsy) within 28 days prior to randomization and not recovered adequately from the
toxicities and/or complications

- Has a gastrointestinal disorder affecting absorption or is unable to swallow
tablets/capsules

- Has an active infection (including tuberculosis) requiring systemic therapy

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV) infection

- Has known or suspected central nervous system (CNS) metastases and/or carcinomatous
meningitis

- Has a history of seizure or any condition that may predispose to seizure

- Has a history of loss of consciousness within 12 months of screening

- Has had myocardial infarction or uncontrolled angina within 6 months prior to
randomization, or has New York Heart Association class III or IV congestive heart
failure or a history of New York Heart Association class III or IV congestive heart
failure

- Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or
uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood
pressure >105 mmHg) at the screening visit

- Has a history of clinically significant ventricular arrhythmias

- Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their
excipients

- Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate
cancer for >39 months in duration or within 9 months prior to randomization or with
evidence of disease progression while receiving ADT

- Has had prior treatment with a next generation hormonal agent (eg, abiraterone,
enzalutamide, apalutamide, darolutamide)

- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand
2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory
T-cell receptor

- Has received a live vaccine within 30 days prior to randomization

- Has a "superscan" bone scan

- Has had an allogenic tissue/solid organ transplant

- Is expecting to conceive or father children within the projected duration of the
study, starting with the screening visit through 120 days after the last dose of study
treatment

- Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic
prostate cancer with the following exceptions:

1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation
antiandrogens, if patient was not treated with docetaxel

2. May have 1 course of palliative radiation or surgical therapy to treat symptoms
resulting from metastatic disease if it was administered at least 4 weeks prior
to randomization

3. For participants with low volume metastatic disease, may have 1 course of
definitive radiotherapy if it was administered at least 4 weeks prior to
randomization

4. Up to 6 cycles of docetaxel therapy with final treatment administration completed
within 2 months of randomization and no evidence of disease progression. In these
participants up to 6 months of ADT permitted