Phase 3 Study of Pembrolizumab plus Enzalutamide in mCRPC

Phase 1

• Conditions: Metastatic Castration-Resistant Prostate Cancer; MedDRA 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-CZ
• Lead Sponsor: Merck Sharp & Dohme Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-03-17
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 1200

Inclusion Criteria

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. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of enzalutamide:
• Refrain from donating sperm PLUS 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), as detailed below:
• Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who

Exclusion Criteria

the participant:
1. Has a 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. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
4. Has a 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 to randomization and not recovered adequately from the toxicities and/or complications
6. Has a gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer disease within last 3 months)
7. Is unable to swallow tablets/capsules
8. Has an active infection (including tuberculosis) requiring systemic therapy
9. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
10. Has known active HIV, concurrent active hepatitis B (defined as HBsAg positive reactive and/or detectable HBV DNA) or known active and hepatitis C virus (defined as anti HCV Ab positive and detectable HCV RNA infection).
11. Has 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 to randomization. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
13. Has a history of seizure or any condition that may predispose to seizure
14. Has a history of loss of consciousness within 12 months of the Screening Visit
15. Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization
16. Has a history of clinically significant ventricular arrhythmias
17. Has a history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
18. Has hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mmHg) at the Screening Visit
19. Has bradycardia as indicated by a heart rate of <50 beats per minute on the Screening electrocardiogram (ECG)
20. Has uncontrolled hypertension as indicated by systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg at the Screening Visit
21. Has

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified