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Clinical Trials List

Protocol NumberMK-7339-010
NCT Number(ClinicalTrials.gov Identfier)NCT03834519
Completed

2019-04-30 - 2024-12-31

Phase III

Recruiting3

Terminated2

ICD-10C61

Malignant neoplasm of prostate

ICD-10Z51.12

Encounter for antineoplastic immunotherapy

ICD-9185

Malignant neoplasm of prostate

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)

  • Trial Applicant

    Merck Sharp & Dohme (I.A.) LLC

  • Sponsor

    Merck Sharp & Dohme Corp.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2026/02/01

Investigators and Locations

Principal Investigator Yi-Hsiu Huang Division of Urology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chao-Hsiang Chang Division of Urology
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chuan-Shu Chen Division of Urology
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator CHUNG-HSIN CHEN Division of Urology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Principal Investigator Wen-Pin Su Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Condition/Disease

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Objectives

Primary Objectives -To compare pembrolizumab plus olaparib to abiraterone acetate or enzalutamide with respect to overall survival (OS) -To compare pembrolizumab plus olaparib to abiraterone acetate or enzalutamide with respect to 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 (BICR)

Test Drug

Keytruda® injection /Lynparza® Film-coated Tablets

Active Ingredient

4-[(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorophenyl)methyl]phthalazin-1(2H)-one
Pembrolizumab (Humanized anti-PD-1 mAb)

Dosage Form

Injection
Film-coated Tablet

Dosage

100
100, 150

Endpoints

Primary Outcome Measures :
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


Secondary Outcome Measures :
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

≥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
≥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

Inclution Criteria

1. Have histologically or cytologically confirmed (if acceptable according to local health
authority regulations) 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. Refer to Section 8.2.2
for further details.
 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 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 through 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 no more than 1 previous chemotherapy regimen for mCRPC and have had
PD during treatment. If docetaxel chemotherapy has been used more than once (eg, once
for metastatic hormone-sensitive prostate cancer and once for mCRPC), 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
(LHRH) 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 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 prior to the date of
randomization.
9. Have adequate organ function as defined in Table 1; 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 (vasectomized or
secondary to medical cause [Appendix 5]) 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 is not currently pregnant. Note: Men with a
pregnant or breastfeeding partner must agree to remain abstinent from penilevaginal intercourse or use a male condom during each episode of penilevaginal penetration.
13. Also agree to use a male condom when engaging in any activity that allows passage of
ejaculate to another person of any sex.
14. The participant (or legally acceptable representative if applicable) provides written
informed consent/assent for the study. The participant may also provide consent/assent
for future biomedical research. However, the participant may participate in the main
study without participating in future biomedical research.
15. Have 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; other exceptions may be considered
after Sponsor consultation. Participants with bone-only or bone-predominant disease
may provide a bone biopsy sample. However, if obtaining a fresh biopsy is not feasible,
participants may provide an archival tumor tissue sample after Sponsor consultation (SCF
submission). Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
Newly obtained biopsies are preferred to archived tissue.
Note: If unstained cut slides are submitted, newly cut slides should be submitted to the
testing laboratory within 14 days from the date they are cut. Details pertaining to tumor
tissue submission are in the Procedures Manual.
16. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
assessed within 7 days of randomization.

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 who have undergone potentially curative
therapy are not excluded.
2. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features
suggestive of MDS/AML.
3. Has persistent toxicities (CTCAE Grade >2) caused by previous cancer therapy,
excluding alopecia and neuropathy.
4. Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant
erythropoietin) within 28 days prior to the date of randomization.
5. Is considered a poor medical risk due to a serious uncontrolled medical disorder,
nonmalignant systemic disease, or active uncontrolled infection. Examples include, but
are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months)
myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord
compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on
high resolution computed tomography scan, or any psychiatric disorder that prohibits
obtaining informed consent.
6. Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the study.
7. Has an active autoimmune disease that has required systemic treatment in the 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.
8. Has a gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer
disease within the last 3 months).
9. Is unable to swallow capsules/tablets.
10. Has a history of (noninfectious) pneumonitis requiring steroids, or has current
pneumonitis.
11. Has an active infection, including tuberculosis, requiring systemic therapy.
12. 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 indicate that participation in the study is not in the
best interest of the participant, in the opinion of the treating investigator.
13. Has known active human immunodeficiency virus (HIV), hepatitis B virus (eg, hepatitis
B surface antigen reactive) or hepatitis C virus (HCV) infection (eg, HCV RNA
[qualitative] is detected). Testing is not required unless mandated by the local health
authority. Refer to Appendix 7 for country-specific testing requirements.
14. 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 28 days
prior to the date of randomization) and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and do not use steroids
for at least 7 days prior to the date of randomization. This exception does not include
carcinomatous meningitis, which is excluded regardless of clinical stability.
15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (at
doses exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the date of randomization.
16. Has severe (Grade >3) hypersensitivity to pembrolizumab and/or any of its excipients.
17. Has known hypersensitivity to the components or excipients in olaparib, abiraterone
acetate, prednisone or prednisolone, or enzalutamide.
18. Has CTCAE Grade ≥2 peripheral neuropathy, except when due to trauma.
19. Has ascites or clinically significant pleural effusion.
20. Has had a seizure or seizures within 6 months of signing the informed consent or has any
condition that may predispose to seizures, including but not limited to prior
cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation,
or intracranial mass such as a schwannoma or meningioma that is causing edema or mass
effect.
21. Has a history of loss of consciousness within 12 months of the screening visit.
22. Has symptomatic congestive heart failure (New York Heart Association Class III or IV
heart disease).
23. Has had a myocardial infarction or uncontrolled angina within 6 months prior to the date
of randomization.
Note: Participants with a recent history of revascularization for acute coronary syndrome
within 3 months prior to the date of randomization will be included.
24. Has a history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, or torsade de pointes).
25. Has a history of Mobitz II second-degree or third-degree heart block without a pacemaker
in place.
26. Has hypotension as indicated by systolic blood pressure (BP) <86 mmHg at the screening
visit.
27. Has bradycardia as indicated by heart rate <50 beats/minute on the screening
electrocardiogram (ECG).
28. Has uncontrolled hypertension as indicated by systolic BP >170 mmHg or diastolic BP
>105 mmHg at the screening visit.
29. Has received an anticancer mAb within 4 weeks prior to the date of randomization, or has
not recovered (ie, Grade ≤1 or baseline) from AEs due to mAbs administered more than 4
weeks prior to the date of randomization.
Note: Treatment with denosumab as standard of care for bone metastases is permitted.
30. Has received prior treatment with olaparib or any other PARP inhibitor.
31. Has received prior treatment with apalutamide or darolutamide.
32. Has received prior treatment with abiraterone acetate for metastatic hormone-sensitive
prostate cancer.
33. Has undergone major surgery, including local prostate intervention (except prostate
biopsy), within 28 days prior to the date of randomization, and has not recovered from
the toxicities and/or complications.
34. Has used herbal products that may have hormonal anti-prostate cancer activity and/or are
known to decrease PSA (eg, saw palmetto) within 4 weeks prior to the date of
randomization.
35. Has received prior treatment with radium or other therapeutic radiopharmaceuticals for
prostate cancer.
36. Has received prior radiotherapy within 2 weeks of the date of randomization.
Participants must have recovered from all radiation-related toxicities, must not require
corticosteroids, and must not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease.
37. 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 (eg, CTLA-4,
OX-40, or CD137).
38. Has received prior targeted small molecule therapy within 4 weeks prior to the date of
randomization or has not recovered (ie, Grade ≤1 or at baseline) from AEs due to a
previously administered agent, with the exceptions of Grade ≤2 neuropathy or Grade ≤2
alopecia.
39. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin,
protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir,
boceprevir, or telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem,
fluconazole, or verapamil) inhibitors of CYP3A4 that cannot be discontinued for the
duration of the study. The required washout period prior to starting olaparib is 2 weeks.
40. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin,
rifabutin, rifapentine, carbamazepine, nevirapine, or St John’s wort) or moderate (eg,
bosentan, efavirenz, or modafinil) inducers of CYP3A4 that cannot be discontinued for
the duration of the study. The required washout period prior to starting olaparib is
5 weeks for phenobarbital and 3 weeks for other agents.
Note: A current list of strong/moderate inhibitors and inducers of CYP3A4 can be found
at the following website:
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugI
nteractionsLabeling
41. Is currently being treated with CYP450-inducing antiepileptic drugs for seizures. Use of
antiepileptic drugs for pain control is allowed in participants without seizures, unless
these drugs are excluded due to CYP450 induction (eg, phenytoin, carbamazepine, and
phenobarbital).
42. Has received 5α reductase inhibitors (eg, finasteride or dutasteride), estrogens, or
cyproterone within 4 weeks prior to the date of randomization.
43. Has received a previous allogenic bone marrow transplant or double umbilical cord
transplantation (dUCBT).
44. Has received a whole blood transfusion in the last 120 days prior to the date of
randomization. Packed red blood cells and platelet transfusions are acceptable if not
given within 28 days of the date of randomization.
45. Has received a live vaccine within 30 days prior to the date of randomization. Examples
of live vaccines include, but are not limited to, measles, mumps, rubella, varicella/zoster
(chicken pox), yellow fever, rabies, bacillus Calmette–Guérin (BCG), and typhoid
vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and
are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
46. 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.
47. Has a resting ECG indicating uncontrolled, potentially reversible cardiac conditions as
judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia,
congestive heart failure, Fridericia-corrected QC interval [QTcF] prolongation
>500 msec, electrolyte disturbances, etc.), or has congenital long QT syndrome.
48. Has a bone “superscan,” defined as intense symmetric activity in bones and diminished
renal parenchymal activity on the baseline bone scan, such that the presence of additional
metastases in the future cannot be evaluated.
49. 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.

The Estimated Number of Participants

  • Taiwan

    35 participants

  • Global

    780 participants

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