Phase 3 Study of Pembrolizumab Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in mCRPC
- Conditions
- Metastatic Castration resistant Prostate Cancer (mCRPC)MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004118-16-NL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 780
1.Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology. The diagnosis must be stated in a pathology report and confirmed by the investigator
2. Have prostate cancer progression while receiving ADT (or post
bilateral orchiectomy) within 6 months before screening, as determined by the investigator through 1 of the following:
-PSA progression shown by local laboratory values, as defined by a
minimum of 2 consecutive rising PSA levels with an interval of =1 week between each assessment, where PSA at screening should be =1 ng/mL.
-Radiographic disease progression in soft tissue based on RECIST 1.1, with or without PSA progression.
-Radiographic disease progression in bone per PCWG, defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression
3.Have disease progression under the following conditions if the
participant received anti-androgen therapy before enrollment:
-Evidence of progression >4 weeks since the last flutamide treatment.
-Evidence of progression >6 weeks since the last bicalutamide or
nilutamide treatment.
4.Have current evidence of metastatic disease documented by bone lesions on bone scan and/or soft tissue disease shown by CT/MRI.
5.Have received prior treatment with abiraterone acetate OR
enzalutamide, but not both
-Have disease that progressed during or after treatment with
abiraterone acetate or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression).
6.Have received docetaxel chemotherapy regimen for mCRPC and have had PD during or after treatment with docetaxel. If docetaxel
chemotherapy has been used more than once, it will be considered as 1 therapy. Prior docetaxel for mCRPC is allowed if =4 weeks have elapsed from the last dose of docetaxel before Day 1 of Cycle 1.
7.Have ongoing androgen deprivation with serum testosterone <50
ng/dL (<2.0 nM). If the participant is currently being treated with
luteinizing hormone-releasing hormone agonists or antagonists (in
participants who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks before the date of randomization, and treatment must be continued throughout the study.
8.If receiving bone resorptive therapy, including but not limited to
bisphosphonates or denosumab, have been receiving stable doses for =4 weeks before the date of randomization.
9.Have adequate organ function; all screening laboratory tests should be performed by the central laboratory within 10 days of the first dose of study intervention
10.Be male
11.Be =18 years of age on the day of signing the informed
consent. Contraceptive use by men should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies
12.Participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception after the last dose of study intervention for each study intervention is as follows:
-olaparib: 95d
-abiraterone acetate: 7d
-enzalutmaide: 30d
-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 confirmed to be azoosp
- 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 the past 2 years
- Has a history of (noninfectious) pneumonitis requiring steroids, or has current pneumonitis
- Has known active human immunodeficiency virus (HIV), hepatitis B virus (e.g., hepatitis B surface antigen reactive) or hepatitis C virus (HCV) infection (e.g., HCV RNA [qualitative] is detected)
- Has known active 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 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- Has (Grade =3) hypersensitivity to pembrolizumab and/or any of its excipients
- Has known hypersensitivity to the components or excipients in olaparib, abiraterone acetate, prednisone or prednisolone, or enzalutamide
- Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
- Has received an anticancer monoclonal antibody (mAb) before randomization
- Has received prior treatment with olaparib or any other PARP inhibitor
- Has received prior treatment with apalutamide or darolutamide
- Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) before the date of randomization
- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
- Has received prior treatment with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor(e.g., CTLA-4, OX-40, or CD137)
- Is currently receiving either strong or moderate inhibitors of cytochrome P450
[CYP] (CYP3A4) that cannot be discontinued for the duration of the study
- Has received a previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) or a solid organ translant
- Has received a live vaccine within 30 days before the date of randomization
- Is currently participating in or has participated in a study of an investigational agent, or has used an investigational device, within 4 weeks before the date of randomization
- Has a bone superscan”
- Is expecting to father children within the projected duration of the study, starting with the screening visit through the duration after the last dose of study intervention listed in inclusion criterion #12
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