Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)

  • STATUS
    Recruiting
  • End date
    Sep 1, 2026
  • participants needed
    1232
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 1 March 2021

Summary

This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS).

Details
Condition Metastatic Hormone Sensitive Prostate Cancer
Treatment Placebo, Pembrolizumab, Enzalutamide, Androgen Deprivation Therapy (ADT)
Clinical Study IdentifierNCT04191096
SponsorMerck Sharp & Dohme Corp.
Last Modified on1 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have any of these conditions: Do you have Metastatic Hormone Sensitive Prostate Cancer??
Do you have Metastatic Hormone Sensitive Prostate Cancer?
Are you male?
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 ADT with a 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 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
Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
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
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
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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note