Phase 3 Study of Pembrolizumab plus Enzalutamide in mCRPC
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004117-40-NL
- Lead Sponsor
- Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 1240
A participant will be eligible for inclusion in the study if the participant:
1. Have histologically- or cytologically-confirmed (if acceptable
according to local health authority regulations) adenocarcinoma of the
prostate without small cell histology. Diagnosis must be stated in a
pathology report and confirmed by the investigator.
2. Have prostate cancer progression while on ADT (or post bilateral
orchiectomy) within 6 months prior to randomization, as determined by
the investigator, by means of one of the following:
a. PSA progression using local laboratory values as defined by a
minimum of 2 consecutive rising PSA levels with an interval of =1 week
between each
assessment where the PSA value at screening should be =1 ng/mL.
b. Radiographic disease progression in soft tissue based on RECIST 1.1
criteria with or without PSA progression.
c. Radiographic disease progression in bone based on PCWG defined as
the appearance of 2 or more new bone lesions on bone scan with or
without PSA progression.
3. Have progression under the following conditions if the participant
received anti-androgen therapy prior to enrollment:
a. Evidence of progression >4 weeks since last flutamide treatment.
b. Evidence of progression >6 weeks since last bicalutamide or
nilutamide treatment.
4. Have current evidence of metastatic disease documented by either
bone lesions on bone scan and/or soft tissue disease by CT/MRI.
Participants whose disease spread is limited to regional pelvic lymph
nodes are not eligible.
5. Have met one of the following criteria with regard to abiraterone
acetate exposure:
a. Not received prior abiraterone acetate (ie, abiraterone naïve)
b. Received prior abiraterone acetate for the treatment of mHSPC or
mCRPC, for a minimum of 4 weeks and must not have progressed while
on treatment.
c. Received prior abiraterone acetate for the treatment of mHSPC or
mCRPC and progressed on treatment after a minimum of 8 weeks
treatment (minimum 14 weeks for those with bone progression).
6. Have ongoing androgen deprivation with serum testosterone <50
ng/mL (<2.0 nM). If the participant is currently being treated with
luteinizing hormone-releasing hormone agonists or antagonists
(participants who have not undergone an orchiectomy) this therapy
must have been initiated at least 4 weeks prior to randomization and
treatment must be continued throughout the study.
7. Participants receiving bone resorptive therapy must have been on
stable doses for =4 weeks prior to randomization.
8. Demonstrate adequate organ function as defined in Protocol; all
screening labs should be performed in central laboratory within 10 days
of the first dose of study intervention.
9. Participant is male.
10. Participant is =18 years of age on day of signing the informed
consent.
11. Participants are eligible to participate if they agree to the following
during the intervention period and for at least 45 days after the last dose
of enzalutamide:
Either:
-Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agree to
remain abstinent
OR
-Must agree to use contraception, unless confirmed to be azoospermic
(vasectomized or secondary to medical cause, documented from the site
personnel's review of the participant's medical records, medical
examination, or medical history interview) as detailed below:
·Agree to use a male condom plus partner use of an additional
contraceptive method when having penile-vagina
1.Known additional malignancy that is progressing or has required active treatment in the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded
2.Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment
3.Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose
4.History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
5.Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior randomization and not recovered
6.Gastrointestinal disorder affecting absorption
7.Unable to swallow tablets/capsules
8.Active infection (including tuberculosis) requiring systemic therapy
9.History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis
10.Known active HIV, concurrent active hepatitis B or known active and hepatitis C virus
11.Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to randomization and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior randomization. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
12.Known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the study
13.History of seizure or any condition that may predispose to seizure
14.History of loss of consciousness within 12 months of Screening Visit
15.Had myocardial infarction or uncontrolled angina within 6 months prior randomization
16.History of clinically significant ventricular arrhythmias
17.History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
18.Hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mmHg) at Screening Visit
19.Bradycardia as indicated by a heart rate of <50 beats/minute on the Screening ECG
20.Uncontrolled hypertension as indicated by systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg at Screening Visit
21.Hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
22.History of prostate cancer progression on ketoconazole
23.Prior treatment with second-generation androgen receptor inhibitor or CYP17 inhibitor other than abiraterone acetate
24.Received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or coinhibitory Tcell receptor
25.Received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
26.Had prior chemotherapy for mCRPC. Prior docetaxel for mHSPC is allowed if more than 4 weeks have elapsed from the last dose of docetaxel
27.Recei
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method