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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 : Completed
First Posted : February 8, 2019
Results First Posted : April 20, 2023
Last Update Posted : February 2, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostatic Neoplasms
Interventions Biological: Pembrolizumab
Drug: Olaparib
Drug: Abiraterone acetate
Drug: Prednisone
Drug: Enzalutamide
Drug: Prednisolone
Enrollment 793
Recruitment Details  
Pre-assignment Details Participants randomized to the next-generation hormonal agent monotherapy (NHA) arm received one of two NHA treatments, per protocol.
Arm/Group Title Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Hide Arm/Group Description Participants received 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). Participants received a single NHA of either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR participants received enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression.
Period Title: Overall Study
Started 529 264
Completed 0 0
Not Completed 529 264
Reason Not Completed
Ongoing             234             111
Withdrawal by Subject             4             7
Death             291             146
Arm/Group Title Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA) Total
Hide Arm/Group Description Participants received 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). Participants received a single NHA of either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR participants received enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression. Total of all reporting groups
Overall Number of Baseline Participants 529 264 793
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 529 participants 264 participants 793 participants
69.9  (7.4) 69.1  (7.3) 69.6  (7.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 529 participants 264 participants 793 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
529
 100.0%
264
 100.0%
793
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 529 participants 264 participants 793 participants
Hispanic or Latino
71
  13.4%
32
  12.1%
103
  13.0%
Not Hispanic or Latino
441
  83.4%
219
  83.0%
660
  83.2%
Unknown or Not Reported
17
   3.2%
13
   4.9%
30
   3.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 529 participants 264 participants 793 participants
American Indian or Alaska Native
1
   0.2%
0
   0.0%
1
   0.1%
Asian
102
  19.3%
59
  22.3%
161
  20.3%
Native Hawaiian or Other Pacific Islander
1
   0.2%
1
   0.4%
2
   0.3%
Black or African American
1
   0.2%
4
   1.5%
5
   0.6%
White
419
  79.2%
199
  75.4%
618
  77.9%
More than one race
1
   0.2%
0
   0.0%
1
   0.1%
Unknown or Not Reported
4
   0.8%
1
   0.4%
5
   0.6%
Measurable Response Evaluation Criteria in Solid Tumors Version 1.1 Disease Status at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 529 participants 264 participants 793 participants
RECIST Measurable: Yes
244
  46.1%
119
  45.1%
363
  45.8%
RECIST Measurable: No
285
  53.9%
145
  54.9%
430
  54.2%
[1]
Measure Description: Measurable disease at baseline is defined as having disease that is Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)-measurable lesions per blinded independent central review (BICR).
Prior Use of NHA Treatment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 529 participants 264 participants 793 participants
Abiraterone only
289
  54.6%
143
  54.2%
432
  54.5%
Enzalutamide only
240
  45.4%
120
  45.5%
360
  45.4%
Abiraterone and Enzalutamide
0
   0.0%
1
   0.4%
1
   0.1%
[1]
Measure Description: Prior use of NHA treatment was defined as prior treatment with Abiraterone only, Enzalutamide only, or Abiraterone and Enzalutamide.
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Time Frame Up to ~31 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Hide Arm/Group Description:
Participants received 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).
Participants received a single NHA of either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR participants received enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression.
Overall Number of Participants Analyzed 529 264
Median (95% Confidence Interval)
Unit of Measure: Months
15.8
(14.6 to 17.0)
14.6
(12.6 to 17.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Olaparib, Next-generation Hormonal Agent Monotherapy (NHA)
Comments Treatment difference in survival assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2616
Comments [Not Specified]
Method Log Rank
Comments One-sided p-value based on log-rank test stratified by measurable disease status and prior NHA treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.77 to 1.14
Estimation Comments Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by measurable disease status and prior NHA treatment.
2.Primary Outcome
Title Radiographic Progression-Free Survival (rPFS)
Hide Description rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions or ≥2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Time Frame Up to ~31 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Hide Arm/Group Description:
Participants received 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).
Participants received a single NHA of either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR participants received enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression.
Overall Number of Participants Analyzed 529 264
Median (95% Confidence Interval)
Unit of Measure: Months
4.4
(4.2 to 6.0)
4.2
(4.0 to 6.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Olaparib, Next-generation Hormonal Agent Monotherapy (NHA)
Comments Treatment difference in rPFS assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5544
Comments [Not Specified]
Method Log Rank
Comments One-sided p-value based on log-rank test stratified by measurable disease status and prior NHA treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.82 to 1.25
Estimation Comments Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by measurable disease status and prior NHA treatment.
3.Secondary Outcome
Title Time to Initiation of the First Subsequent Anticancer Therapy (TFST)
Hide Description TFST is the time from randomization to initiation of the first subsequent anticancer therapy defined as the first anti-cancer treatment not part of the study arm for a given participant, or death, whichever occurs first. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions per RECIST 1.1 and no evidence of disease (NED) bone scan) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 and Non-PD, non-evaluable (NE), or NED bone scan or CR with non-PD or NE bone scan.) The percentage of participants who experienced CR or PR as assessed by BICR is presented.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥ 2 new bone lesions is also considered PD. DOR as assessed by BICR is presented.
Time Frame Up to ~24 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time to Prostate-Specific Antigen (PSA) Progression
Hide Description

Time to PSA progression is defined as the 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. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Time to First Symptomatic Skeletal-Related Event (SSRE)
Hide Description

SSRE is defined as the time from randomization to the first symptomatic skeletal-related event, defined as whichever occurs first:

  • 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
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Time to Radiographic Soft Tissue Progression
Hide Description Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression per soft tissue rule of PCWG-modified RECIST 1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Time to radiographic soft tissue progression as assessed by BICR is presented.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Time to Pain Progression (TTPP)
Hide Description

TTPP is defined as 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.

Pain progression is defined as:

  1. For participants who are asymptomatic at baseline, a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain
  2. For participants who are symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids), a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits.

Participants who had more than 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Number of Participants Who Experience an Adverse Event (AE)
Hide Description 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. The number of participants who experienced an adverse event are presented.
Time Frame Up to ~31 months
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Hide Description The number of participants who discontinue study treatment due to an AE are presented.
Time Frame Up to ~880 Days
Outcome Measure Data Not Reported
Time Frame For All-Cause Mortality: from allocation up to ~31 months. For AEs from start of treatment up to ~31 months.
Adverse Event Reporting Description All-cause mortality: All allocated participants. AEs: All allocated participants who received ≥1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. The next-generation hormonal agent monotherapy interventions are considered standard of care (SOC).
 
Arm/Group Title Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Hide Arm/Group Description Participants received 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). Participants received a single NHA of either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR participants received enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression.
All-Cause Mortality
Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Affected / at Risk (%) Affected / at Risk (%)
Total   293/529 (55.39%)      149/264 (56.44%)    
Hide Serious Adverse Events
Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   168/526 (31.94%)      55/256 (21.48%)    
Blood and lymphatic system disorders     
Anaemia † 1  18/526 (3.42%)  20 3/256 (1.17%)  3
Anaemia of malignant disease † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Febrile neutropenia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pancytopenia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Thrombocytopenia † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Cardiac disorders     
Acute myocardial infarction † 1  3/526 (0.57%)  3 0/256 (0.00%)  0
Atrial fibrillation † 1  2/526 (0.38%)  4 0/256 (0.00%)  0
Cardiac failure † 1  4/526 (0.76%)  4 1/256 (0.39%)  1
Cardiac failure chronic † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Cardiac failure congestive † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Cardiogenic shock † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Coronary artery disease † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Coronary artery occlusion † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Coronary artery stenosis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Myocardial infarction † 1  4/526 (0.76%)  4 0/256 (0.00%)  0
Myocarditis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Ear and labyrinth disorders     
Vertigo † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Endocrine disorders     
Adrenal insufficiency † 1  9/526 (1.71%)  9 1/256 (0.39%)  1
Hypothyroidism † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Eye disorders     
Diplopia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Abdominal pain upper † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Colitis † 1  4/526 (0.76%)  4 0/256 (0.00%)  0
Diarrhoea † 1  4/526 (0.76%)  4 0/256 (0.00%)  0
Dysphagia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Gastric ulcer † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Gastrointestinal haemorrhage † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Gastrooesophageal reflux disease † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Haematemesis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Inguinal hernia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Mechanical ileus † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Melaena † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Nausea † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Neutropenic colitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Oesophageal haemorrhage † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pneumoperitoneum † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Rectal haemorrhage † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Subileus † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Vomiting † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
General disorders     
Asthenia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Death † 1  3/526 (0.57%)  3 2/256 (0.78%)  2
Fatigue † 1  2/526 (0.38%)  2 1/256 (0.39%)  1
General physical health deterioration † 1  4/526 (0.76%)  4 0/256 (0.00%)  0
Malaise † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Multiple organ dysfunction syndrome † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Pain † 1  1/526 (0.19%)  1 2/256 (0.78%)  2
Pyrexia † 1  4/526 (0.76%)  4 0/256 (0.00%)  0
Systemic inflammatory response syndrome † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hepatobiliary disorders     
Autoimmune hepatitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Bile duct stone † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Gallbladder disorder † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hepatic function abnormal † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Immune-mediated hepatitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Immune system disorders     
Anaphylactic reaction † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Cytokine release syndrome † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Infections and infestations     
Appendicitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Atypical pneumonia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Bacteraemia † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
COVID-19 † 1  5/526 (0.95%)  5 1/256 (0.39%)  1
COVID-19 pneumonia † 1  4/526 (0.76%)  4 2/256 (0.78%)  2
Clostridium difficile colitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Dengue fever † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Device related infection † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Encephalitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Erysipelas † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Herpes zoster † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Infective spondylitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Kidney infection † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Oral candidiasis † 1  1/526 (0.19%)  2 0/256 (0.00%)  0
Periodontitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pneumocystis jirovecii pneumonia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pneumonia † 1  15/526 (2.85%)  15 2/256 (0.78%)  2
Pneumonia aspiration † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Prostatitis Escherichia coli † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Pyelonephritis † 1  4/526 (0.76%)  4 3/256 (1.17%)  3
Sepsis † 1  3/526 (0.57%)  3 1/256 (0.39%)  1
Septic shock † 1  5/526 (0.95%)  5 0/256 (0.00%)  0
Streptococcal bacteraemia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Urinary tract infection † 1  10/526 (1.90%)  11 4/256 (1.56%)  4
Urosepsis † 1  0/526 (0.00%)  0 2/256 (0.78%)  2
Injury, poisoning and procedural complications     
Accidental overdose † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Contusion † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Craniocerebral injury † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Fall † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Femoral neck fracture † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Femur fracture † 1  2/526 (0.38%)  2 1/256 (0.39%)  1
Fracture † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Gastroenteritis radiation † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hand fracture † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Ilium fracture † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Lumbar vertebral fracture † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Post-traumatic pain † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Radiation proctitis † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Spinal fracture † 1  1/526 (0.19%)  1 1/256 (0.39%)  1
Subdural haematoma † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Thermal burn † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Thoracic vertebral fracture † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Toxicity to various agents † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Investigations     
Aspartate aminotransferase increased † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Blood creatine phosphokinase increased † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Blood creatinine increased † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Neutrophil count decreased † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
SARS-CoV-2 test positive † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Dehydration † 1  3/526 (0.57%)  3 0/256 (0.00%)  0
Diabetes mellitus † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Electrolyte imbalance † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hypocalcaemia † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Hyponatraemia † 1  1/526 (0.19%)  1 3/256 (1.17%)  3
Type 1 diabetes mellitus † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Musculoskeletal and connective tissue disorders     
Back pain † 1  7/526 (1.33%)  7 2/256 (0.78%)  2
Bone pain † 1  3/526 (0.57%)  3 0/256 (0.00%)  0
Lumbar spinal stenosis † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Musculoskeletal chest pain † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Myositis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Osteonecrosis of jaw † 1  1/526 (0.19%)  1 2/256 (0.78%)  2
Pain in extremity † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Polyarthritis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Polymyalgia rheumatica † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Spinal pain † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Spinal stenosis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Transitional cell carcinoma † 1  0/526 (0.00%)  0 2/256 (0.78%)  2
Tumour pain † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Nervous system disorders     
Cerebral ischaemia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Cerebrovascular accident † 1  3/526 (0.57%)  3 0/256 (0.00%)  0
Depressed level of consciousness † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Ischaemic stroke † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Paraparesis † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Paraplegia † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Presyncope † 1  1/526 (0.19%)  1 1/256 (0.39%)  1
Sciatica † 1  1/526 (0.19%)  1 1/256 (0.39%)  1
Seizure † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Spinal cord compression † 1  5/526 (0.95%)  5 0/256 (0.00%)  0
Syncope † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Transient ischaemic attack † 1  1/526 (0.19%)  1 1/256 (0.39%)  1
Psychiatric disorders     
Confusional state † 1  2/526 (0.38%)  2 1/256 (0.39%)  1
Renal and urinary disorders     
Acute kidney injury † 1  3/526 (0.57%)  3 1/256 (0.39%)  1
Haematuria † 1  3/526 (0.57%)  4 4/256 (1.56%)  4
Haemorrhage urinary tract † 1  1/526 (0.19%)  3 0/256 (0.00%)  0
Hydronephrosis † 1  1/526 (0.19%)  1 1/256 (0.39%)  1
Nephrolithiasis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Postrenal failure † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pyelocaliectasis † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Renal colic † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Renal failure † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Renal impairment † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Ureteric stenosis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Ureterolithiasis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Urinary retention † 1  5/526 (0.95%)  6 2/256 (0.78%)  3
Urinary tract obstruction † 1  4/526 (0.76%)  4 1/256 (0.39%)  1
Respiratory, thoracic and mediastinal disorders     
Immune-mediated lung disease † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Interstitial lung disease † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pleural effusion † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pneumomediastinum † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pneumonitis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Pulmonary embolism † 1  3/526 (0.57%)  3 0/256 (0.00%)  0
Skin and subcutaneous tissue disorders     
Drug eruption † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Psoriasis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Toxic epidermal necrolysis † 1  0/526 (0.00%)  0 1/256 (0.39%)  1
Toxic skin eruption † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Vascular disorders     
Aortic aneurysm † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Deep vein thrombosis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Embolism † 1  2/526 (0.38%)  2 0/256 (0.00%)  0
Hypertension † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hypertensive crisis † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
Hypotension † 1  1/526 (0.19%)  1 0/256 (0.00%)  0
1
Term from vocabulary, MedDRA 24.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab + Olaparib Next-generation Hormonal Agent Monotherapy (NHA)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   490/526 (93.16%)      212/256 (82.81%)    
Blood and lymphatic system disorders     
Anaemia † 1  271/526 (51.52%)  322 35/256 (13.67%)  37
Endocrine disorders     
Hypothyroidism † 1  52/526 (9.89%)  53 4/256 (1.56%)  4
Gastrointestinal disorders     
Constipation † 1  100/526 (19.01%)  112 42/256 (16.41%)  45
Diarrhoea † 1  101/526 (19.20%)  129 22/256 (8.59%)  26
Nausea † 1  221/526 (42.02%)  272 45/256 (17.58%)  49
Vomiting † 1  90/526 (17.11%)  143 18/256 (7.03%)  20
General disorders     
Asthenia † 1  92/526 (17.49%)  106 26/256 (10.16%)  28
Fatigue † 1  184/526 (34.98%)  195 66/256 (25.78%)  67
Oedema peripheral † 1  44/526 (8.37%)  48 14/256 (5.47%)  15
Pyrexia † 1  50/526 (9.51%)  57 7/256 (2.73%)  8
Infections and infestations     
Urinary tract infection † 1  26/526 (4.94%)  33 13/256 (5.08%)  16
Investigations     
Alanine aminotransferase increased † 1  27/526 (5.13%)  28 7/256 (2.73%)  7
Aspartate aminotransferase increased † 1  36/526 (6.84%)  44 10/256 (3.91%)  10
Blood alkaline phosphatase increased † 1  32/526 (6.08%)  33 24/256 (9.38%)  27
Blood creatinine increased † 1  44/526 (8.37%)  51 6/256 (2.34%)  6
Weight decreased † 1  65/526 (12.36%)  67 15/256 (5.86%)  15
Metabolism and nutrition disorders     
Decreased appetite † 1  150/526 (28.52%)  169 44/256 (17.19%)  50
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  94/526 (17.87%)  115 37/256 (14.45%)  46
Back pain † 1  81/526 (15.40%)  91 43/256 (16.80%)  48
Bone pain † 1  34/526 (6.46%)  42 25/256 (9.77%)  26
Myalgia † 1  33/526 (6.27%)  35 8/256 (3.13%)  10
Pain in extremity † 1  33/526 (6.27%)  37 23/256 (8.98%)  31
Nervous system disorders     
Dizziness † 1  43/526 (8.17%)  51 9/256 (3.52%)  9
Dysgeusia † 1  31/526 (5.89%)  32 3/256 (1.17%)  3
Headache † 1  29/526 (5.51%)  36 13/256 (5.08%)  19
Psychiatric disorders     
Insomnia † 1  23/526 (4.37%)  25 13/256 (5.08%)  14
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1  42/526 (7.98%)  51 9/256 (3.52%)  10
Skin and subcutaneous tissue disorders     
Pruritus † 1  41/526 (7.79%)  46 6/256 (2.34%)  6
Rash † 1  38/526 (7.22%)  49 3/256 (1.17%)  3
Vascular disorders     
Hot flush † 1  11/526 (2.09%)  11 16/256 (6.25%)  16
Hypertension † 1  27/526 (5.13%)  33 31/256 (12.11%)  32
1
Term from vocabulary, MedDRA 24.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: Clinicaltrialsdisclosure@merck.com
Publications of Results:
Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, Massari F, Suzuki H, Qiu P, Zhang J, Kim J, Poehlein CH, Yu EY. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. J Clin Oncol. 2023 Aug 1;41(22):3839-3850. doi: 10.1200/JCO.23.00233. Epub 2023 Jun 8.
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT03834519    
Other Study ID Numbers: 7339-010
MK-7339-010 ( Other Identifier: Merck Protocol Number )
KEYLYNK-010 ( Other Identifier: Merck )
2018-004118-16 ( EudraCT Number )
First Submitted: February 6, 2019
First Posted: February 8, 2019
Results First Submitted: March 2, 2023
Results First Posted: April 20, 2023
Last Update Posted: February 2, 2024