Phase 3 Study of Pembrolizumab Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in mCRPC

Phase 1

• Conditions: Metastatic Castration resistant Prostate Cancer (mCRPC); MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004118-16-GB
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-13
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 780

Inclusion Criteria

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 androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to 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 prior to screening:
-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 for either mHSPC or mCRPC or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression).
Patients that received abiraterone acetate for mHSPC may not have received abiraterone acetate or enzalutamide for mCRPC.
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 prior to 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 prior to the date of randomization, and treatment must be continued hroughout the study.
8.If receiving bone resorptive therapy, including but not limited to bisphosphonates or denosumab, have been receiving stable doses for =4 weeks prior to the date of randomization.
9.Have adequate organ function per central laboratory; 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.Agree to the following during the intervention period and for at least 180 days,corresponding to the time needed to eliminate 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:
-Agree to use contraception unless confirmed to be azoospermic
or
-Secondary to medical cause as detailed: Agree to

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 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) prior to 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) prior to 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 transplant
- Has received a live vaccine within 30 days prior to 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 prior to 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 180 days after the last dose of study intervention

Study & Design

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