Phase 3
Completed N=793
Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)
Prostatic Neoplasms
Source: ClinicalTrials.gov NCT03834519 ↗
Enrolled (actual)
793
Serious AEs
30.4%
Results posted
Apr 2023
Primary outcomePrimary: Overall Survival (OS) — 15.8; 14.6 Months — p=0.2616
◆ Published Evidence
Highly cited
131citations · ~44 / year
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.
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)
As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable. Participants still on treatment may have the option to continue receiving study intervention or SOC if they are deriving clinical benefit, until criteria for discontinuation are met. Participants who are still on study treatment and deriving clinical benefit will no longer have tumor response assessments by BICR. However, local tumor imaging assessments should continue per standard of care (SOC) schedule. In addition, electronic patient-reported outcome (ePRO) assessments will no longer be performed and biomarker samples will no longer be collected.
Linked Publications (2)
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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.
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Patient-reported Outcomes in KEYLYNK-010: Pembrolizumab Plus Olaparib Versus Abiraterone or Enzalutamide for Participants with Biomarker-unselected, Previously Treated Metastatic Castration-resistant Prostate Cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
15.8; 14.6 | 0.2616 |
| PRIMARY Radiographic Progression-Free Survival (rPFS) |
4.4; 4.2 | 0.5544 |
| SECONDARY Time to Initiation of the First Subsequent Anticancer Therapy (TFST) |
7.2; 5.7 | — |
| SECONDARY Objective Response Rate (ORR) |
16.8; 5.9 | — |
| SECONDARY Duration of Response (DOR) |
8.1; 8.5 | — |
| SECONDARY Time to Prostate-Specific Antigen (PSA) Progression |
3.3; 3.5 | — |
| SECONDARY Time to First Symptomatic Skeletal-Related Event (SSRE) |
NA; NA | — |
| SECONDARY Time to Radiographic Soft Tissue Progression |
10.3; 6.4 | — |
| SECONDARY Time to Pain Progression (TTPP) |
13.5; 12.0 | 0.3643 |
| SECONDARY Number of Participants Who Experience an Adverse Event (AE) |
518; 238 | — |
| SECONDARY Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) |
90; 11 | — |
Eligibility Criteria
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 before 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 metastatic castration-resistant prostate cancer (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 before randomization
- Must agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic
- Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirement above, the local label requirements are to be followed.
- 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) before 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 prosta
Data sourced from ClinicalTrials.gov (NCT03834519) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.