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Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

Primary Purpose

Merkel Cell Carcinoma

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab (MK-3475)
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Merkel Cell Carcinoma focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Merkel cell carcinoma

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be male or female and at least 12 years of age, at the time of signing the informed consent/assent.
  • Have histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV) as per American Joint Committee on Cancer (AJCC) 8th edition guidelines.
  • Have been untreated for advanced or metastatic disease except as follows:

    1. Prior intratumoral therapy will be permitted.
    2. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to Cycle 1 Day 1 (C1D1).
    3. Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy will not be permitted.
  • Have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment.
  • Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia).
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP)
  • OR
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis).
  • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky Play-Performance Scale (LPS) ≥50 for pediatric participants up to and including 16 years of age.
  • Have adequate organ function

Exclusion Criteria:

  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years with certain exceptions.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis with certain exceptions.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to C1D1.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Has clinically significant cardiac disease within 6 months of C1D1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
  • 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 is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  • Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease. Note: This exclusion criterion does not apply to participants who are diagnosed with unresectable or metastatic MCC.
  • Has received prior therapy 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.
  • Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1.
  • Has received radiotherapy within 2 weeks prior to start of study intervention.
  • Has received a live vaccine within 30 days prior to C1D1.
  • 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 C1D1.
  • Has had an allogenic tissue/solid organ transplant.

Sites / Locations

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0006)
  • Icahn School of Medicine at Mount Sinai ( Site 0004)
  • Melanoma Institute Australia ( Site 0400)
  • Calvary Mater Newcastle ( Site 0402)
  • Moncton Hospital - Horizon Health Network ( Site 0055)
  • Princess Margaret Cancer Centre ( Site 0051)
  • Hopital de la Cote de Nacre - Caen ( Site 0204)
  • CHU de Bordeaux- Hopital Saint Andre ( Site 0203)
  • Hopital Ambroise Pare Boulogne ( Site 0201)
  • C.H.R.U. de Tours. Hopital Trousseau ( Site 0202)
  • CHRU Lille - Hopital Claude Huriez ( Site 0200)
  • Azienda Ospedaliera Universitaria Senese ( Site 0224)
  • IEO Istituto Europeo di Oncologia ( Site 0223)
  • Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)
  • Istituto Oncologico Veneto ( Site 0221)
  • Auckland City Hospital ( Site 0427)
  • Hospital General Universitario de Valencia ( Site 0262)
  • Hospital Universitari Vall d Hebron ( Site 0264)
  • Hospital Clinic de Barcelona ( Site 0261)
  • Hospital Universitario La Paz ( Site 0263)
  • Karolinska Universitetssjukhuset Solna ( Site 0281)
  • Sahlgrenska Universitetssjukhuset ( Site 0282)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab

Arm Description

Pembrolizumab (MK-3475) 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) intravenous (IV), for up to 35 administrations (approximately 2 years)

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by blinded independent central review (BICR) were presented.

Secondary Outcome Measures

Duration of Response (DOR)
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.
Progression-free Survival (PFS)
Progression-Free Survival is defined as the time from the first dose of study treatment to the first documented evidence of disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per 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 demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR per RECIST 1.1 will be presented.
Overall Survival (OS)
OS is defined as the time from the first dose of study treatment until death from any cause.
Number of Participants With One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE will be assessed.
Number of Participants Who Discontinued From Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue from study treatment due to an AE will be assessed.

Full Information

First Posted
December 19, 2018
Last Updated
January 25, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03783078
Brief Title
Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)
Official Title
A Phase 3 Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) as First Line Therapy in Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-913)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2019 (Actual)
Primary Completion Date
February 15, 2022 (Actual)
Study Completion Date
June 16, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a single-arm, open-label, multicenter, efficacy, and safety study of pembrolizumab in adult and pediatric participants with previously untreated advanced Merkel Cell Carcinoma (MCC). The primary objective of the trial is to assess the objective response rate, as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following administration of pembrolizumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Merkel Cell Carcinoma
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Merkel cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab
Arm Type
Experimental
Arm Description
Pembrolizumab (MK-3475) 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) intravenous (IV), for up to 35 administrations (approximately 2 years)
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab (MK-3475)
Other Intervention Name(s)
MK-3475
Intervention Description
200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) IV up to 35 administrations (approximately 2 years).
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by blinded independent central review (BICR) were presented.
Time Frame
Up to ~34 months
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.
Time Frame
Up to ~13 years
Title
Progression-free Survival (PFS)
Description
Progression-Free Survival is defined as the time from the first dose of study treatment to the first documented evidence of disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per 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 demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR per RECIST 1.1 will be presented.
Time Frame
Up to ~13 years
Title
Overall Survival (OS)
Description
OS is defined as the time from the first dose of study treatment until death from any cause.
Time Frame
Up to ~13 years
Title
Number of Participants With One or More Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE will be assessed.
Time Frame
Up to ~13 years
Title
Number of Participants Who Discontinued From Study Treatment Due to an AE
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue from study treatment due to an AE will be assessed.
Time Frame
Up to ~13 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be male or female and at least 12 years of age, at the time of signing the informed consent/assent. Have histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV) as per American Joint Committee on Cancer (AJCC) 8th edition guidelines. Have been untreated for advanced or metastatic disease except as follows: Prior intratumoral therapy will be permitted. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to Cycle 1 Day 1 (C1D1). Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy will not be permitted. Have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment. Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia). Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis). A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky Play-Performance Scale (LPS) ≥50 for pediatric participants up to and including 16 years of age. Have adequate organ function Exclusion Criteria: Has a known additional malignancy that is progressing or has required active treatment within the past 2 years with certain exceptions. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis with certain exceptions. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to C1D1. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has an active infection requiring systemic therapy. Has a known history of human immunodeficiency virus (HIV) infection. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). Has clinically significant cardiac disease within 6 months of C1D1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. 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 is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease. Note: This exclusion criterion does not apply to participants who are diagnosed with unresectable or metastatic MCC. Has received prior therapy 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. Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1. Has received radiotherapy within 2 weeks prior to start of study intervention. Has received a live vaccine within 30 days prior to C1D1. 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 C1D1. Has had an allogenic tissue/solid organ transplant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0006)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai ( Site 0004)
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Melanoma Institute Australia ( Site 0400)
City
North Sydney
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Calvary Mater Newcastle ( Site 0402)
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Moncton Hospital - Horizon Health Network ( Site 0055)
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 6Z8
Country
Canada
Facility Name
Princess Margaret Cancer Centre ( Site 0051)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hopital de la Cote de Nacre - Caen ( Site 0204)
City
Caen
State/Province
Calvados
ZIP/Postal Code
14033
Country
France
Facility Name
CHU de Bordeaux- Hopital Saint Andre ( Site 0203)
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33000
Country
France
Facility Name
Hopital Ambroise Pare Boulogne ( Site 0201)
City
Boulogne-Billancourt
State/Province
Hauts-de-Seine
ZIP/Postal Code
92100
Country
France
Facility Name
C.H.R.U. de Tours. Hopital Trousseau ( Site 0202)
City
Chambray Les Tours
State/Province
Indre-et-Loire
ZIP/Postal Code
37170
Country
France
Facility Name
CHRU Lille - Hopital Claude Huriez ( Site 0200)
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Facility Name
Azienda Ospedaliera Universitaria Senese ( Site 0224)
City
Siena
State/Province
Toscana
ZIP/Postal Code
53100
Country
Italy
Facility Name
IEO Istituto Europeo di Oncologia ( Site 0223)
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Istituto Oncologico Veneto ( Site 0221)
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Auckland City Hospital ( Site 0427)
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Hospital General Universitario de Valencia ( Site 0262)
City
Valencia
State/Province
Valenciana, Comunitat
ZIP/Postal Code
46014
Country
Spain
Facility Name
Hospital Universitari Vall d Hebron ( Site 0264)
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona ( Site 0261)
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario La Paz ( Site 0263)
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Karolinska Universitetssjukhuset Solna ( Site 0281)
City
Solna
State/Province
Stockholms Lan
ZIP/Postal Code
171 64
Country
Sweden
Facility Name
Sahlgrenska Universitetssjukhuset ( Site 0282)
City
Goeteborg
State/Province
Vastra Gotalands Lan
ZIP/Postal Code
413 45
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

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