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JOURNAL ONKOLOGIE – STUDIE
KEYLYNK-010

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

Rekrutierend

NCT-Nummer:
NCT03834519

Studienbeginn:
Mai 2019

Letztes Update:
29.04.2021

Wirkstoff:
Pembrolizumab, Olaparib, abiraterone acetate, Prednisone, Enzalutamide

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 192)

Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4976127028930
» Ansprechpartner anzeigen
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
90419 Nuernberg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49911398114729
» Ansprechpartner anzeigen
Tulane Cancer Center ( Site 0066)
70112 New Orleans
United StatesAbgeschlossen» Google-Maps
UMass Memorial Medical Center ( Site 0053)
01655 Worcester
United StatesAbgeschlossen» Google-Maps
Barbara Ann Karmanos Cancer Institute ( Site 0077)
48201 Detroit
United StatesAbgeschlossen» Google-Maps
St. Vincent Frontier Cancer Center ( Site 0016)
59102 Billings
United StatesAbgeschlossen» Google-Maps
Nebraska Cancer Specialists ( Site 0034)
68130 Omaha
United StatesAbgeschlossen» Google-Maps
Memorial Medical Center ( Site 0095)
88011 Las Cruces
United StatesAbgeschlossen» Google-Maps
The Urology Group- Cincinnati ( Site 0094)
45212 Cincinnati
United StatesAbgeschlossen» Google-Maps
Virginia Cancer Institute ( Site 0052)
23230 Richmond
United StatesAbgeschlossen» Google-Maps
Blue Ridge Cancer Care ( Site 0086)
24014 Roanoke
United StatesAbgeschlossen» Google-Maps
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
B1884BBF Berazategui
ArgentinaAktiv, nicht rekrutierend» Google-Maps
CEMAIC ( Site 1014)
X5008HHW Cordoba
ArgentinaAktiv, nicht rekrutierend» Google-Maps
St. Vincent's Hospital ( Site 0158)
2010 Darlinghurst
AustraliaAbgeschlossen» Google-Maps
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
90610-000 Porto Alegre
BrazilRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +555133203039
» Ansprechpartner anzeigen
Clinique Sainte Anne ( Site 0431)
67000 Strasbourg
FranceAktiv, nicht rekrutierend» Google-Maps
Centre Leon Berard ( Site 0422)
69373 Lyon
FranceAktiv, nicht rekrutierend» Google-Maps
Institut Paoli Calmettes ( Site 0419)
13009 Marseille
FranceAktiv, nicht rekrutierend» Google-Maps
CHU Jean Minjoz ( Site 0423)
25000 Besancon
FranceAktiv, nicht rekrutierend» Google-Maps
CHU de Brest -Site Hopital Morvan ( Site 0441)
29200 Brest
FranceAktiv, nicht rekrutierend» Google-Maps
Institut Bergonie ( Site 0421)
33076 Bordeaux
FranceAktiv, nicht rekrutierend» Google-Maps
Centre D Oncologie de Gentilly ( Site 0432)
54100 Nancy
FranceAktiv, nicht rekrutierend» Google-Maps
C.H.U. Lyon Sud ( Site 0436)
69310 Pierre Benite
FranceAktiv, nicht rekrutierend» Google-Maps
Institut Sainte Catherine ( Site 0447)
84000 Avignon
FranceAktiv, nicht rekrutierend» Google-Maps
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79219697575
» Ansprechpartner anzeigen
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79219629807
» Ansprechpartner anzeigen
Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)
634028 Tomsk
Russian FederationAbgeschlossen» Google-Maps
Hospital Quiron Madrid ( Site 0325)
28223 Pozuelo de Alarcon
SpainAbgeschlossen» Google-Maps
Hospital del Mar ( Site 0333)
08003 Barcelona
SpainAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

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)

Ein-/Ausschlusskriterien

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 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 90 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

- 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 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) before 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 before 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 90 days after the last dose of study intervention

Studien-Rationale

Primary outcome:

1. Overall Survival (OS) (Time Frame - Up to approximately 29 months):
Time from randomization to death due to any cause

2. 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:

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

Studien-Arme

  • 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).
  • 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 OR two 80 mg tablets QD until progression.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion
  • Olaparib (MK-7339 / AZD-2281 / LYNPARZA® / ):
    Oral tablets
  • Abiraterone acetate (ZYTIGA® / CB-7630 / JNJ-212082 / ):
    Oral tablets
  • Prednisone:
    Oral tablets
  • Enzalutamide (XTANDI® / MDV-3100 / ASP-9785 / ):
    Oral tablets or oral capsules

Quelle: ClinicalTrials.gov


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