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Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010) (KEYLYNK-010)

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ClinicalTrials.gov Identifier: NCT03834519
Recruitment Status : Recruiting
First Posted : February 8, 2019
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE February 6, 2019
First Posted Date  ICMJE February 8, 2019
Last Update Posted Date January 21, 2020
Actual Study Start Date  ICMJE May 2, 2019
Estimated Primary Completion Date October 12, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2019)
  • Overall Survival (OS) [ Time Frame: Up to approximately 29 months ]
    Time from randomization to death due to any cause
  • Radiographic Progression-Free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Time from randomization to radiographic progression, or death due to any cause, whichever occurs first
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03834519 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • Time to Initiation of the First Subsequent Anticancer Therapy (TFST) [ Time Frame: Up to approximately 29 months ]
    Time from randomization to initiation of the first subsequent anticancer therapy
  • Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1
  • Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Time from first documented evidence of confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first
  • Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to approximately 29 months ]
    Time from randomization to PSA progression. PSA progression date is defined as the date of
    1. ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, OR
    2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline
  • Time to First Symptomatic Skeletal-Related Event (SSRE) [ Time Frame: Up to approximately 29 months ]
    Time to first SSRE: the time from randomization to the first symptomatic skeletal-related event, defined as:
    • First use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms;
    • Occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral);
    • Occurrence of spinal cord compression; or
    • Tumor-related orthopedic surgical intervention, whichever occurs first
  • Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Time to radiographic soft tissue progression: the time from randomization to radiographic soft tissue progression
  • Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score) [ Time Frame: Up to approximately 29 months ]
    TTPP: the time from randomization to pain progression as determined by Item 3 of the Brief Pain Inventory Short Form (BPI-SF) and by the Analgesic Quantification Algorithm (AQA) score
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 29 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment
  • Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 29 months ]
    The number of participants who discontinue study treatment due to an AE will be presented
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2019)
  • Time to Initiation of the First Subsequent Anticancer Therapy or Death (TFST) [ Time Frame: Up to approximately 29 months ]
    Time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first
  • Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1
  • Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Time from first documented evidence of confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first
  • Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to approximately 29 months ]
    Time from randomization to PSA progression. PSA progression date is defined as the date of
    1. ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, OR
    2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline
  • Time to First Symptomatic Skeletal-Related Event (SSRE) [ Time Frame: Up to approximately 29 months ]
    Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone
  • Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 29 months ]
    Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1
  • Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score) [ Time Frame: Up to approximately 29 months ]
    Time from randomization to pain progression. In this study, pain progression will be assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 29 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment
  • Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 29 months ]
    The number of participants who discontinue study treatment due to an AE will be presented
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)
Official Title  ICMJE A Phase 3, Randomized Open-label Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Who Are Unselected for Homologous Recombination Repair Defects and Have Failed Prior Treatment With One Next-generation Hormonal Agent (NHA) and Chemotherapy (KEYLYNK-010)
Brief Summary

The purpose of this study is to assess the efficacy and safety of the combination of the polyadenosine 5'-diphosphoribose poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and pembrolizumab in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate or enzalutamide (but not both) and to chemotherapy.

The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to:

  1. Overall Survival (OS) and
  2. Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 as assessed by blinded independent central review (BICR)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Olaparib
    Oral tablets
    Other Names:
    • MK-7339
    • AZD-2281
    • LYNPARZA®
  • Drug: Abiraterone acetate
    Oral tablets
    Other Names:
    • ZYTIGA®
    • CB-7630
    • JNJ-212082
  • Drug: Prednisone
    Oral tablets
  • Drug: Enzalutamide
    Oral tablets or oral capsules
    Other Names:
    • XTANDI®
    • MDV-3100
    • ASP-9785
Study Arms  ICMJE
  • Experimental: Pembrolizumab + Olaparib
    Participants receive olaparib 600 mg as two 150 mg oral tablets twice daily (BID) continuously until progression PLUS on Day 1 of each 21-day cycle, pembrolizumab 200 mg by intravenous (IV) infusion for up to 35 cycles (approximately 2 years).
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Olaparib
  • Active Comparator: Abiraterone + Prednisone or Enzalutamide
    Participants receive abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone 10 mg as one 5 mg tablet BID until progression OR Participants receive enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules QD until progression.
    Interventions:
    • Drug: Abiraterone acetate
    • Drug: Prednisone
    • Drug: Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2019)
780
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date October 12, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
  • Has prostate cancer progression while receiving androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to screening
  • Has current evidence of metastatic disease documented by bone lesions on bone scan and/or soft tissue disease shown by computed tomography/magnetic resonance imaging (CT/MRI)
  • Has received prior treatment with abiraterone acetate OR enzalutamide, but not both

    • Have disease that progressed during or after treatment with abiraterone acetate for either metastatic hormone-sensitive prostate cancer (mHSPC) or mCRP or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression)
    • Participants that received abiraterone acetate for mHSPC may not have received abiraterone acetate or enzalutamide for mCRPC
  • Have received docetaxel chemotherapy regimen for mCRPC and have had progressive disease during or after treatment with docetaxel
  • Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
  • If receiving bone resorptive therapy, including but not limited to bisphosphonates or denosumab, must have been receiving stable doses prior to randomization
  • Must agree to refrain from donating sperm during the intervention period and for at least 180 days thereafter PLUS Be abstinent from heterosexual intercourse OR Agree to use contraception unless confirmed to be azoospermic AND Also agree to use a male condom when engaging in any activity that allows passage of ejaculate to another person of any sex
  • Has provided tumor tissue from a fresh core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization

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 received prior treatment with enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Brazil,   Canada,   Chile,   France,   Germany,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03834519
Other Study ID Numbers  ICMJE 7339-010
2018-004118-16 ( EudraCT Number )
MK-7339-010 ( Other Identifier: Merck Protocol Number )
KEYLYNK-010 ( Other Identifier: Merck )
194832 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP