Phase 3 Study of Pembrolizumab/Placebo plus Enzalutamide plus ADT in mHSPC

Phase 1

• Conditions: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC); 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: PTClassification code 10071119Term: Hormone-dependent prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003633-41-AT
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-13
• Last Update Posted: 3 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 1232

Inclusion Criteria

1. Has 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. Has metastatic disease as assessed by investigator and verified by BICR (prior to randomization) by either =2 bone lesions on bone scan and/or visceral disease (eg, lung or liver) by CT/MRI. Participants whose metastatic disease is limited to lymph nodes are not eligible.
3. Once randomized, participant must be willing to maintain continuous ADT with a LHRH agonists or antagonists during study treatment or have a history of bilateral orchiectomy.
4. Has an ECOG performance status of 0 or 1 assessed within 10 days of randomization.
5. Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for =4 weeks prior to randomization.
6. Demonstrates adequate organ function; all screening labs should be performed in central laboratory within 10 days of the first dose of study intervention.
7. Is male, =18 years of age at the time of signing the informed consent.
8. Male participants are eligible to participate if they 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 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 WOCBP who is not currently pregnant.
9. 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.
10. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study.
11. 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; other exceptions may be considered after Sponsor consultation). Participants with bone only or bone predominant disease may provide a bone biopsy sample (decalcification not allowed). However, if obtaining a new biopsy is not feasible, then participants may provide an archival tumor tissue sample after Sponsor consultation (SCF). FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archive tissue. Adequacy of these specimens for PD-L1 biomarker analysis will be required by a central laboratory prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 406
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 826

Exclusion Criteria

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. Replacement therapy is not considered a form of systemic treatment.
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) 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.
7. Is unable to swallow tablets/capsules.
8. Has an active infection (including tuberculosis) requiring systemic therapy.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
10. Has known active HIV, hepatitis B virus or HCV. Testing for Hepatitis B and Hepatitis C is not required unless mandated by local regulation.
11. Has known or suspected CNS metastases and/or carcinomatous meningitis.
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 (including, but not limited to prior cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation; or intracranial masses such as a schwannoma or meningioma that is causing edema or mass effect).
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 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 unless a screening echocardiogram or multigated acquisition scan performed within 3 months prior to randomization date demonstrates a left ventricular ejection fraction >45%.
17. Has a history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes).
18. Has a history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
19. Has hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mmHg) at the Screening Visit.
20. Has bradycardia as indicated by a heart rate of <50 beats per minute on the Screening ECG.
21. Has uncontrolled hypertension as indicated by systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg at the Screening visit.
22. Has severe hypersensitivity (Grade =3) to pembrolizumab and/or any of its excipients.
23. Has hypersensitivity reaction to enzalutamide or any of its capsule components, including Labrasol, but

Study & Design

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